Washing Machine Pralka automatyczna Pln automatick praka Skalbimo maina
WML 15105 D WML 15085 D WML 15065 D WML 15045 D

1 Warnings

Never place your machine on a carpet covered floor. Otherwise, lack of airflow from below of your machine may cause electrical parts to overheat. This may cause problems with your washing machine. If the power cable or mains plug is damaged you must call Authorized Service for repair. Fit the drain hose into the discharge housing securely to prevent any water leakage and to allow machine to take in and discharge water as required. It is very important that the water intake and drain hoses are not folded, squeezed, or broken when the appliance is pushed into place after it is installed or cleaned. Your washing machine is designed to continue operating in the event of a power interruption. Your machine will not resume its program when the power restores. Press the Start/Pause/Cancel button for 3 seconds to cancel the program (See, Canceling a Program) There may be some water in your machine when you receive it. This is from the quality control process and is normal. It is not harmful to your machine. Some problems you may encounter may be caused by the infrastructure. Press "Start/Pause/Cancel" button for 3 seconds to cancel the program set in your machine before calling the authorized service.

General Safety

Intended use
by classifying according to waste directives.
This product has been designed for home use. The appliance may only be used for washing and rinsing of textiles that are marked accordingly.

Safety instructions

First Use
Carry out your first washing process without loading your machine and with detergent under Cottons 90C program. Ensure that the cold and hot water connections are made correctly when installing your machine. If the current fuse or circuit breaker is less than 16 Amperes, please have a qualified electrician install a 16 Ampere fuse or circuit breaker. While using with or without a transformer, do not neglect to have the grounding installation laid by a qualified electrician. Our company shall not be liable for any damages that may arise when the machine is used on a line without grounding. Keep the packaging materials out of reach of children or dispose them
This appliance must be connected to an earthed outlet protected by a fuse of suitable capacity. The supply and draining hoses must always be securely fastened and remain in an undamaged state. Fit the draining hose to a washbasin or bathtub securely before starting up your machine. There may be a risk of being scalded due to high washing temperatures! Never open the loading door or remove the filter while there is still water in the drum. Unplug the machine when it is not in use. Never wash down the appliance with a water hose! There is the risk of electric shock! Never touch the plug with wet hands. Do not operate the machine if the power cord or plug is damaged. For malfunctions that cannot be solved by information in the operating manual: Turn off the machine, unplug it, turn off the water tap and contact an authorized service agent. You may refer to your local agent or solid waste collection center in your municipality to learn how to dispose of your machine. Keep children away from the machine when it is operating. Do not let them tamper with the machine. Close the loading door when you leave the area where the machine is located.
If there are children in your house.

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2 Installation
Removing packaging reinforcement
Tilt the machine to remove the packaging reinforcement. Remove the packaging reinforcement by pulling the ribbon.
ATransportation safety bolts must be removed before operating the washing machine! Otherwise, the machine will be damaged! 1. Loosen all the bolts with a spanner until they rotate freely (C) 2. Remove transportation safety bolts by turning them gently. 3. Fit the covers (supplied in the bag with the Operation Manual) into the holes on the rear panel. (P)
Opening the transportation locks
CKeep the transportation safety bolts in a safe place to reuse when the washing machine needs to be moved again in the future. CNever move the appliance without the transportation safety bolts properly fixed in place! ADo not use any tools to loosen the lock nuts. Otherwise, they can be damaged. 1. Manually (by hand) loosen the lock nuts on the feet. 2. Adjust them until the machine stands level and firmly. 3. Important: Tighten all lock nuts up again.
there are rubber seals (4 seals for the models with double water inlet and 2 seals for other models) attached to the hoses. These seals should be used at the tap and machine connection ends of the hoses. The plain end of the hose fitted with a filter must be attached to the tap and the elbowed end must be attached to the machine. Tighten the nuts of the hose well by hand; never use wrenches to tighten the nuts. Models with a single water inlet should not be connected to the hot water tap. When returning the appliance to its place after maintenance or cleaning, care should be taken not to fold, squeeze or block the hoses.

Connecting to the drain

Adjusting the feet
The water discharge hose can be attached to the edge of a washbasin or bathtub. The drain hose should be firmly fitted into the drain as to not get out of its housing. Important: The end of the drain hose must be directly connected to the wastewater drain or to the washbasin. The hose should be attached to a height of at least 40 cm, and 100 cm at most. In case the hose is elevated after laying it on the floor level or close to the ground (less than 40 cm above the ground), water discharge
Connecting to the water supply.
Important: The water supply pressure required to run the machine must be 1-10 bar (0,MPa). Connect the special hoses supplied with the machine to the water intake valves on the machine. In order to prevent water leakage that may occur at the connection points,
becomes more difficult and the laundry may come out wet. The hose should be pushed into the drainage for more than 15 cm. If it is too long you may have it shortened. 3 - EN
The maximum length of the combined hoses must not be longer than 3.2 m.

Correct load capacity

CPlease follow the information in the

Loading door

Electrical connection
Connect the machine to an earthed outlet protected by a fuse of suitable capacity. Important: Connection should comply with national regulations. The voltage and the allowed fuse protection are specified in the section Technical Specifications. The specified voltage must be equal to your mains voltage. Connection via extension cords or multi-plugs should not be made. BA damaged power cable must be replaced by a qualified electrician. BThe appliance must not be operated unless it is repaired! There is the risk of electric shock!
Program Selection Table. Washing results will degrade when the machine is overloaded.
The door locks during program operation and the Door Locked Symbol (Figure 3-13i) lights up. The door can be opened when the symbol fades out.

Detergents and softeners

Detergent Drawer
The detergent drawer is composed of three compartments: The detergent dispenser may be in two different types according to the model of your machine. (I) for prewash (II) for main wash - (III) siphon ( ) for softener

3 Initial preparations for washing
Preparing clothes for washing
Laundry items with metal attachments such as, bras, belt buckles and metal buttons will damage the machine. Remove metal attachments or place the items in a clothing bag, pillow case, or something similar. Sort the laundry according to type of fabric, color, and degree of soiling and permissible water temperature. Always follow the advice on the garment labels. Place small items like infants socks and nylon stockings, etc. in a laundry bag, pillow case or something similar. This will also save your laundry from getting lost. Wash machine washable or hand washable labeled products only with an appropriate program. Do not wash colors and whites together. New, dark colored cottons may release a lot of dye. Wash them separately. Use only dyes/color changers and lime removers suitable for machine wash. Always follow the instructions on the packaging. Wash trousers and delicate clothes turned inside out.
Detergent, softener and other cleaning agents
Add detergent and softener before starting the washing program. Never open the detergent dispenser drawer while the washing program is running! When using a program without pre-wash, no detergent should be put into the prewash compartment (Compartment no. I).

Detergent quantity

The amount of washing detergent to be used depends on the amount of laundry, the degree of soiling and water hardness. Do not use amounts exceeding the quantities recommended on the package to avoid problems of excessive foam, poor rinsing, financial savings and finally, environmental protection. Never exceed the (> max <) level marking; otherwise, the softener will be wasted without being used. Do not use liquid detergent if you want to wash using the time delay feature.

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4 Selecting a program and operating your machine

Control panel

1000 500

3 Reset

- 2 - 3 - 4 - 5 - Spin Speed Adjustment Knob * Temperature Adjustment Button * Start/Pause/Cancel Button Auxiliary Function Keys Program Selection Knob 6 - On/Off Button 7 - Program Follow-up Indicators 8 - Child-proof Lock Indicator *
* According to your machines model

Turning the machine on

You can prepare the machine for program selection by pressing the On/Off button. When the On/Off button is pressed, the Ready light illuminates indicating that the door is ulocked. Press the On/Off button again to shut down the machine.

60C 40C30CCold

Normally soiled, fade proof colored linens, cottons or synthetic clothes and lightly soiled white linens Blended clothes including synthetics and woolens as well as delicate clothes.

Program selection

C Programs are limited with the highest
spin speed appropriate for that particular type of cloth.

Main programs Cottons

Select the appropriate program from the program table and the following washing temperature table according to type, amount and degree of soiling of the laundry. Select the desired program with the program selection button. CEach of these programs consist of a complete washing process, including wash, rinse and, if required, spin cycles. 90C Normally soiled, white cottons and linens.
Depending on the type of textile, the following main programs are available: You can wash your durable clothes with this program. Your laundry will be washed with vigorous washing movements during a longer washing cycle.

Synthetics

You can wash your less durable clothes on this program. Gentler washing movements and a shorter washing cycle is used 5 - EN
compared to the Cottons program. It is recommended for your synthetic clothes (such as shirts, blouses, synthetic/cotton blended garments, etc.). For curtains and lace, the Synthetic 40 program with prewash and anti-creasing functions selected is recommended.

Delicates

Spin Speed selection
You can wash your delicate clothes on this program. It has more sensitive washing movements and does not make intermediate spinning compared to Synthetic program.

Woolens

You can wash your machine-washable woolen garments on this program. Wash by selecting the proper temperature according to the labels of your clothes. It is recommended to use appropriate detergents for woolens.

Hand Wash

You can have your clothes spun at the maximum rpm selection on your machine by using the selection knob in models equipped with an rpm selection knob. In order to protect your clothes, your machine will not spin above 800 rpm on synthetic programs and 600 rpm on woolens program. Furthermore, if you want to skip the spin cycle and take your clothes out, turn the rpm selection knob to no spin position. In machines not equipped with a spin speed selection knob, the machine will spin in the maximum possible rpm in the default setting of the selected program.
You can wash your woolen/delicate clothes that bear not machine- washable labels for which hand wash is recommended on this program. It washes the laundry with very tender washing movements without damaging your clothes.

Additional programs

For special cases, there are also extra programs available: C Additional programs may differ according to the model of your machine.

Super

This program washes for a longer period at 40C and gives the same result as the Cottons 60C program, thus it saves energy. It is suitable for clothes for which you cannot use the Cotton 60C program.

This program is used to quickly wash (30 minutes) a small amount of lightly soiled cotton garments.

Special programs

Rinse
For specific applications, you can select any of the following programs: This program is used when you want to rinse or starch separately.

Pump + Spin

This program spins with maximum possible rpm in the default setting after the water drains from the machine. CYou should use a lower spin speed for delicate laundries. 6 - EN
Program selection and consumption table
Programme Duration (~min) Energy Consumption (kWh)

Water Consumption (l)

Max. Load (kg)

Programme

Spin speed reduction

Rinse Hold

Rinse Plus

Prewash

Cottons Cottons Cottons Super Synthetics Synthetics Synthetics Delicate Woollens Hand wash Mini

90 60** 30

2.5 2.5 2.1.2.5
1.65 0.95 0.69 0.78 0.92 0.56 0.30 0.36 0.36 0.21 0.17
: Selectable * : Automatically selected, not cancellable. **: Energy Label programme (EN 60456) Water and power consumption and programme duration may differ from the table shown, subject to changes in water pressure, water hardness and temperature, ambient temperature, type and amount of laundry, selection of auxiliary functions, and fluctuations in the supply voltage.
CThe auxiliary functions in the table may differ according to the model of your

machine. 7 - EN

No Heat

No Spin

Auxiliary functions

Reducing Speed

Auxiliary function selection keys
Select the required auxiliary functions before starting the program. CAuxiliary function buttons may differ according to the model of your machine.
Auxiliary function selection
You may use the speed reduction button whenever you wish to spin your clothes below the maximum spin speed. When speed reduction button is pressed, spin speed will be at the minimum rpm given on the panel.

No spin

If an auxiliary function that should not be selected together with a previously selected function is chosen, the first selected function will be cancelled and the last auxiliary function selection will remain active. For example: If you want to select pre-wash first and then quick wash, pre-wash will be cancelled and quick wash will remain active. Auxiliary function that is not compatible with the program cannot be selected. (see Program Selection Table)

Pre-wash

You may use this program if you do not want to spin your clothes at the end of cottons, synthetics, woolen or delicate programs.

No Heat

If you wish to wash your clothes in cold water, you can use this program.

Starting the Program

Press Start/Pause/Cancel button to start the program. Start/Pause/Cancel button will light up to indicate that the program has started. The door is locked and the Lid light fades.
A pre-wash is only worthwhile for heavily soiled laundry. Without pre-wash you save energy, water, detergent and time. Prewash without detergent is recommended for lace and curtains.

Progressing a program

With this function, you can increase the number of current rinsing steps. Thus, sensitive skins risk of being affected by the remainder detergent on the clothes will be decreased.

Rinse hold

If you do not want to unload your clothes immediately after the cotton, synthetics, woolen and delicate fabrics program, you may release your clothes inside the machine in the last rinsing water by pressing the rinse hold button in order to prevent your clothes become wrinkled. After this process you may spin your laundry by pressing Start/ Pause/Cancel button or you may end the program by pressing Start/Pause/Cancel button for 3 sec. In the machines equipped with spin speed selection knob or button, you can spin by selecting the desired spin speed and press Start/Pause/ Cancel button. As for machines not equipped with a spin speed selection knob, you can end the program without a spin cycle by pressing the Start/Pause/Cancel button and draining the water. If you wish your clothes be spun, you can spin them by selecting pump+spin program.
Progress of a running program is shown through the program follow-up indicator. At the beginning of every program step, the relevant indicator lamp will light up and light of the completed step will turn off. CIf the machine is not spinning, the program may be in rinse hold mode or the automatic spin correction system has been activated because of excessive unbalanced distribution of laundry in the machine.
Changing the selections after the program has started
You can use this feature after your machine has started to wash different textile groups in the same batch of clothes under higher or lower temperatures. You must cancel the ongoing program in order to change the washing program. For example, press and hold the Start/ Pause/Cancel button for 3 seconds to Cancel the program in order to select Cottons 40 program instead of Cottons 60 program. Select the Cottons 40 program by rotating the program knob. Press Start/Pause/Cancel button to start the program.

Switching the machine to standby mode Press Start/Pause/Cancel button momentarily to switch your machine to the standby mode. Auxiliary functions can be

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cancelled or selected in accordance with the step the program is at. The door can be opened if the water level is suitable. Laundry may be added / taken out by opening the door.
5 Maintenance and cleaning
Remove any powder residue buildup in the drawer. To do this; 1. Press the dotted point on the siphon in the softener compartment and pull towards you until the compartment is removed from the machine.

Child-proof lock

You can protect the appliance from being tampered by children by means of the childproof lock. In this case, no change can be made in the running program. The machine is switched to child-lock by pressing the 1st and 2nd auxiliary functions from the left for 3 sec. 1st auxiliary function light will flash continuously. To deactivate the child-proof lock, press the same buttons for 3 sec.
Ending the program through canceling
In order to cancel the selected program, press the Start/Pause/Cancel button for 3 seconds. The machine starts to discharge the water. Wash and Program Finished lights will light up. Start/Pause/Cancel and Wash lights will go off after discharging process is over and the Lid light will start flashing. Lid lamp will light up continuously when the door is unlocked. If the program is cancelled in the middle of the process, Wash and Program Finished lights will light up. The machine can drain all the water or can take in water for 3 times at most to cool down the clothes and complete draining process. When the water discharging process is completed, the Wash light will go off, the Program Finished light will light up and the Lid light will continuously flash until the door is unlocked.

End of program

CIf more than a normal amount of water and softener mixture starts to gather in the softener compartment, the siphon must be cleaned. 2. Wash the dispenser drawer and the siphon with plenty of lukewarm water in a washbasin. 3. Replace the drawer into its housing after cleaning. Check if the siphon is in its original location.

Inlet water filters

There is a filter at the end of each water intake valve at the back side of the machine and also at the end of each water intake hose where they are connected to the tap. These filters prevent the foreign substances and dirt in the water to enter into the machine. Filters should be cleaned as they get dirty.
The Program Finished lamp on the program follow-up indicator will light up when the program comes to an end. The lid is unlocked 2 minutes later, the Program Finished and Lid lamps will light up continuously. The machine is now ready for a second cycle. If any key is pressed when the machine is at the end of the program or if the position of the selection knob is changed, the Program Finished light will go off and only the Lid lamp will remain as lit. If the door is still locked, the Lid light will continue flashing until the door is unlocked. Press the On/Off button to shut down the machine.
Close the taps. Remove the nuts of the water intake hoses to clean the surfaces of the filters on the water intake valves with an appropriate brush. If the filters are very dirty, you can pull them out by means of pliers and clean them. Take out the filters on the flat ends of the water intake hoses together with the gaskets and clean thoroughly under streaming water. Replace the gaskets and filters

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carefully to their places and tighten the hose nuts by hand.
Draining any remaining water and cleaning the pump filter
Your product is equipped with a filter system which ensures a cleaner water discharge that extends pump life by preventing solid items such as buttons, coins and fabric fibers from clogging the pump propeller during discharge of the washing water. If your machine fails to drain the water, the pump filter may be clogged. You may have to clean it every 2 years or whenever it is plugged. Water must be drained off to clean the pump filter. In addition, water may have to be drained off completely in the following cases: before transporting the machine (e.g. when moving house) when there is the danger of frost In order to clean the dirty filter and discharge the water; 1- Unplug the machine to cut off the supply power. AThere may be water at 90C in the machine. Therefore, the filter must be cleaned only after the inside water is cooled down to avoid hazard of scalding. 2- Open the filter cap. The filter cap may be composed of one or two pieces according to the model of your machine. If it is composed of two pieces, press the tab on the filter cap downwards and pull the piece out towards yourself. If it is composed of one piece, hold it from both sides and open it by pulling out.
Place a large container at the end of the hose. Drain the water off into the container by pulling out the plug at the end of the hose. If the amount of water to be drained off is greater than the volume of the container, replace the plug, pour the water out, then resume the draining process. After draining process is completed, replace the plug into the end of the hose and fit the hose back into its place. If your product is not supplied with an emergency drain hose, do the following as shown in the figure below:

3- An emergency drain hose is supplied with some of our models. Others are not supplied with this item. If your product is supplied with an emergency drain hose, do the following as shown in the figure below: Pull out the pump outlet hose from its housing.
Place a large container in front of the filter to receive water flowing from the filter. Loosen pump filter (anticlockwise) until water starts to flow out of it. Direct the flowing water into the container you have placed in front of the filter. You can use a piece of cloth to absorb any spilled water. When there is no water left, turn the pump filter until it is completely loose and remove it. Clean any residues inside the filter as well as fibers, if any, around the propeller region. If your product has a water jet feature, be sure to fit the filter into its housing in the pump. Never force the filter while replacing it into its housing. Fit the filter fully into its housing; otherwise, water may leak from the filter cap. 4- Close the filter cap. Close the two-piece filter cap of your product by pushing the tab on it. Close the one-piece filter cap of your product by fitting the tabs on the bottom into their positions and pushing the upper part of it.

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6 Solution suggestions for problems
Cause Machine may have Program cannot switched to self due to protection mode be started or an infrastructure problem selected. (such as line voltage, water pressure, etc.). There is water coming from the bottom of the machine. Machine stopped shortly after the program started. There might be problems with hoses or the pump filter. Machine can stop temporarily due to low voltage. Problem Explanation / Suggestion Reset your machine by pressing Start/Pause/ Cancel button for 3 seconds. (see, Canceling a Program) Be sure the seals of the water inlet hoses are securely fitted. Tightly attach the drain hose to the tap. Make sure that the pump filter is completely closed. It will resume operating when the voltage is back to the normal level.
The automatic spin correction system might have been activated due to the unbalanced distribution of the laundry in the drum. It continuously The laundry in the drum may be clustered spins. There may be an imbalance (bundled laundry in a bag). Laundry should be Remaining time of laundry in the machine. rearranged and re-spun. does not count No spinning is performed when the laundry is down. not evenly distributed in the drum to prevent any damage to the machine and to its environment. In the case of a paused countdown while taking in The machine will wait until there is a sufficient water: amount of water to avoid poor washing results Timer will not countdown due to lack of water. Then the timer will start to until the machine is filled with the correct amount of count down. water. In the case of a paused countdown at the heating It continuously step: will not count Time washes. Remaining time down until the selected does not count temperature for the program is reached down. The automatic spin correction system might have been activated due to the unbalanced distribution of the laundry in the drum. In the case of a paused countdown at the spinning The laundry in the drum may be clustered be (bundled laundry in a bag). Laundry should step: There may be an imbalance rearranged and re-spun. when the laundry is No spinning is performed of laundry in the machine. not evenly distributed in the drum to prevent any damage to the machine and to its environment.

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7 Specifications
WML 15105 D WML 15085 D WML 15065 D WML 15045 D V / 50hz 400
Shirt Hand wash Cold Child Conditioner lock
Models Maximum dry laundry capacity (kg) Height (cm) Width (cm) Depth (cm) Net Weight (kg) Electricity (V/Hz.) Total Current (A) Total Power (W) Spinning cycle (rpm max.)
230 V / 50hz 230 V / 50hz 230 V / 50hz 600
Specifications of this appliance may change without notice to improve the quality of the product. Figures in this manual are schematic and may not match your product exactly. Values stated on the machine labels or in the documentation accompanying it are obtained in laboratory in accordance with the relevant standards. Depending on operational and environmental conditions of the appliance, values may vary.
This appliances packaging material is recyclable. Help recycle it and protect the environment by dropping it off in the municipal receptacles provided for this purpose. Your appliance also contains a great amount of recyclable material. It is marked with this label to indicate the used appliances that should not be mixed with other waste. This way, the appliance recycling organised by your manufacturer will be done under the best possible conditions, in compliance with European Directive 2002/96/EC on Waste Electrical and Electronic Equipment. Contact your town hall or your retailer for the used appliance collection points closest to your home. We thank you doing your part to protect the environment.
Coton Synthetics Woollens Delicate Babycare Sport

On/Off

Start Pause

Reset 3sn.

Intensive

Express

Quick wash

Anti creasing

Rinse plus
Time Temperature No heat delay

Main wash

Door ready

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1 Ostrzeenia

Wskazwki bezpieczestwa

Nie wolno ustawia pralki na wykadzinie dywanowej. W przeciwnym wypadku brak cyrkulacji powietrza pod spodem pralki moe spowodowa przegrzanie czci elektrycznych. A to z kolei moe prowadzi do wystpienia usterek. W przypadku uszkodzenia kabla zasilajcego lub wtyczki, naley zgosi si do autoryzowanego serwisu w celu wykonania naprawy. Dokadnie przymocowa w spustowy do obudowy, aby zapobiec ewentualnym wyciekom wody oraz zapewni pobr i odpyw wody zalenie od wymogw programu prania. Wana wskazwka w dopywu wody oraz w spustowy nie moe by zagity, poskrcany lub przerwany, gdy urzdzenie jest umieszczone na swoim miejscu po instalacji lub czyszczeniu. Pralka jest zaprojektowana w taki sposb, aby kontynuowa prac w przypadku przerwy w zasilaniu energi elektryczn. Po wznowieniu zasilania pralka bdzie konynuowa pranie od momentu, w ktrym zakoczya przed awari zasilania. Jeli pranie zostao wyjte w trakcie przerwy w zasilaniu naley zanulowa program. Naley nacisn przycisk Start/Pause/ Cancel [Start/Pauza/Kasowanie] na 3 sekundy, aby skasowa program (Patrz, Kasowanie programu) W zakupionej pralce moe znajdowa si niewielka ilo wody. To pozostao po przeprowadzonym tecie kontroli jakoci i jest to zjawisko normalne. Pralka nie ulega przez to uszkodzeniu. Niektre problemy, na ktre napotka uytkownik, mog by spowodowane przez infrastruktur. Naley nacisn przycisk "Start/Pause/Cancel" na 3 sekundy, aby skasowa ustawienia programu w pralce przed telefonicznym zgoszeniem usterki w autoryzowanym serwisie.

Thomas Ernst, PhD Linda Chang, MD Mallory Witt, MD Irwin Walot, MD Howard Aronow, MD Maria Leonido-Yee, MD Elyse Singer, MD
Index terms: Acquired immunodeficiency syndrome (AIDS), 10.2068 Brain, atrophy, 10.83 Brain, diseases, 10.87 Brain, infection, 10.2068 Brain, white matter, 10.87 Magnetic resonance (MR), magnetization transfer contrast, 10.121417 Radiology 1999; 210:539543 Abbreviations: AIDS acquired immunodeficiency syndrome FLAIR fluid-attenuated inversion recovery HIV human immunodeficiency virus PML progressive multifocal leukoencephalopathy WML white matter lesions
Progressive Multifocal Leukoencephalopathy and Human Immunodeficiency Virusassociated White Matter Lesions in AIDS: Magnetization Transfer MR Imaging1
PURPOSE: To determine the magnetization transfer features of progressive multifocal leukoencephalopathy (PML) and human immunodeficiency virus (HIV) associated white matter lesions (WML) (hereafter, HIV-WML) on magnetic resonance (MR) images obtained in patients with acquired immunodeficiency syndrome (AIDS). MATERIALS AND METHODS: Conventional MR imaging and magnetization transfer MR imaging were performed in 21 AIDS patients with 42 areas of white matter hyperintensity on MR images (13 patients had 25 PML lesions, eight patients had 17 WML). The magnetization transfer ratio was calculated for each lesion. RESULTS: Compared with normal-appearing white matter (magnetization transfer ratio 47.9%), both PML and HIV-WML showed reduced magnetization transfer ratio. The magnetization transfer ratio was significantly lower in PML lesions (magnetization transfer ratio 26.1%) than in HIV-WML (magnetization transfer ratio 38.0%, P .0001), and there was no overlap in the magnetization transfer ratio between PML lesions and HIV-WML. The separation in magnetization transfer ratio between the two lesion types was valid for lesions as small as 0.5 cm2. CONCLUSION: The larger reduction in magnetization transfer ratio for PML lesions is most likely due to demyelination, whereas the reduction in HIV-WML may be associated primarily with gliosis. PML lesions appear to cause strong reductions in magnetization transfer ratio early in the course of disease. Magnetization transfer MR imaging is a noninvasive tool that improves the differentiation between PML and HIV-WML in patients with AIDS.
From the Departments of Radiology (T.E., I.W.), Neurology (T.E., L.C., M.L.Y.), and Medicine (M.W.), HarborUCLA Medical Center, 1124 W Carson St, N-11, Torrance, CA 90502; the Departments of Neurology and Medicine, University of Southern California Medical School, Los Angeles (H.A.); and the Department of Neurology, Westwood VA Medical Center, Los Angeles, Calif (E.S.). Received March 20, 1998; revision requested June 16; revision received July 15; accepted September 28. Supported in part by grants from the State of California Universitywide AIDS Research Program to the UCLA CARE Center (CC97 LA 175). L.C. supported in part by the Scientist Development Award for Clinicians DA 00280 from the National Institutes of Health. Address reprint requests to T.E. RSNA, 1999
Author contributions: Guarantor of integrity of entire study, T.E.; study concepts and design, T.E., L.C.; definition of intellectual content, T.E., L.C.; literature research, T.E.; clinical studies, L.C., M.W., H.A., M.L.Y., E.S.; data acquisition and analysis, T.E., I.W.; statistical analysis, T.E.; manuscript preparation, T.E., L.C.; manuscript editing, T.E.; manuscript review, T.E., L.C., M.W.
Magnetic resonance (MR) imaging is the preferred diagnostic technique for the evaluation of patients with acquired immunodeficiency syndrome (AIDS) who have neurologic symptoms. Whereas MR imaging is very sensitive in detecting brain abnormalities, it lacks specificity with respect to the degree of brain injury and may not be able to differentiate between gliosis, demyelination, and edema. Some of these problems might be resolved with magnetization transfer MR imaging, a relatively new contrast mechanism that promises to be more specific for myelin destruction than is T2-weighted MR imaging. Magnetization transfer makes it possible to observe and quantify the exchange of magnetization between water molecules bound to macromolecules (bound water pool) and a free (unbound) water pool. Because of (dipolar) interactions between the two water pools, magnetization may be transferred from the bound to the unbound water pool, eventually changing the observable MR signal from the protons of the free pool (1). In the brain, magnetization transfer is very low for cerebrospinal fluid, moderate for gray matter, and highest for white matter. It has been suggested that the high magnetization transfer of

white matter reflects the high concentration of myelin (14). As a result, demyelinating lesions, such as multiple sclerosis plaques (2,3,5) or progressive multifocal leukoencephalopathy (PML) lesions (6,7), cause dramatic reductions in magnetization transfer. The purpose of this study was to examine the magnetization transfer features of two frequently observed white matter abnormalities in patients with AIDS. The first type of lesions is nonspecific, welldefined white matter lesions (WML) frequently found in the brain of AIDS patients without known opportunistic infections. These human immunodeficiency virus (HIV)associated WML (hereafter, HIV-WML) may be associated with the direct sequelae of HIV and are often nonspecific (8), but they appear to occur more frequently in patients with more advanced AIDS. PML is another common cause of white matter abnormalities in patients with AIDS, affecting 2%7% of all AIDS patients (913). PML is caused by infection of oligodendrocytes by JC virus; low CD4 cell count (100 cells per microliter) is postulated to permit reactivation of latent JC virus (14). PML lesions produce characteristic WML on MR images as well as histopathologic examination (12,1521); however, atypical features are common (12,19,2225). Because PML is a demyelinating disease, we hypothesized that PML lesions would lead to greater reduction in magnetization transfer than would HIV-WML. If this is correct, then magnetization transfer would be useful for improving the differential diagnosis of PML and HIVWML in patients with AIDS. Furthermore, our goal was to determine whether the magnetization transfer values of the lesions are dependent on the size of the lesions.
Figure 1. Graphs depict dependence of (a) average and (b) minimum magnetization transfer ratio (MTR) values on lesion size and lesion type. There is no overlap in magnetization transfer ratios between HIV-WML () and PML lesions () (P .0001 for both variables). In the PML group, one lesion with an area of 11.6 cm2 is not shown.
MATERIALS AND METHODS Patients and Lesions
We prospectively studied 21 AIDS patients with findings in clinical variables and imaging studies consistent with either PML or HIV-WML. Disease in 13 patients (age range, 3357 years) was diagnosed as PML, on the basis of characteristic clinical signs and course, typical MR imaging and MR spectroscopy patterns (25,26), and polymerase chain reaction for JC virus DNA in the cerebrospinal fluid. Six of the PML patients had positive cerebrospinal fluidpolymerase chain reaction for JC virus DNA, and two more patients underwent brain biopsy to confirm the diagnosis of PML. At the time

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of MR imaging, the PML patients had a median duration of PML-related symptoms of 3 months (range, 136 months), a median duration of HIV diagnosis of 52 months (range, 1135 months), and an average CD4 count of 110 cells per microliter 135 (SD) (range, 2420 cells per microliter). Disease in eight patients, aged 3554 years, was diagnosed as HIV-WML. Patients with HIV-WML were asymptomatic, and cerebrospinal fluid showed no signs of bacterial, fungal, or viral infections (with negative polymerase chain reaction for JC virus DNA and negative polymerase chain reaction for cytomegalovirus). In the HIV-WML group, the median duration of HIV diagnosis was 108 months (range, 0.5174.0 months), and the average CD4 count was (range, 20668; median, 135) cells per microliter. Lesions with an area greater than 0.5 cm2 were included in the analysis. Twentyfive lesions were analyzed in the PML group and 17 in the HIV-WML group. All HIV-WML were well-defined hyperintense lesions in the centrum semiovale on T2-weighted or fluid-attenuated inversion recovery (FLAIR) images. Oral or written informed consent was obtained from all patients before MR imaging. The protocol was approved by the institutional review board.
MR imaging consisted of sagittal T1weighted imaging (repetition time msec/ echo time msec 500/11, 5-mm section thickness, 2-mm gap, 24-cm field of view), axial fast double spin-echo imaging (4,000/ 17, 102; 5-mm section thickness; contiguous; 24-cm field of view), and optimized axial FLAIR imaging (11,000/142/2,600 [inversion time msec], 5-mm section thickness, contiguous, 24-cm field of view) (27). Magnetization transfer MR imaging was performed with an axial T1-weighted spinecho sequence (11/650, 5-mm section thickness, contiguous, 24-cm field of view, 4-minute imaging time) that was performed both with and without off-resonance saturation pulses. The offset frequency of the magnetization transfer pulses was 600 Hz.

Image Analysis

Image analysis was performed on a workstation (Alpha; Digital Equipment, Nashua, NH) by means of programs (Interactive Data Language, or IDL; Research Systems, Boulder, Colo) customized specifically for the analysis of magnetization transfer data sets. Data for images with (M1) and without (M0) magnetization transfersaturation pulses were sent to the workstation. For each pixel, the magnetization transfer ratio (MTR) was calculated as the difference in signal intensity between the images without and with magnetization transfer, divided by the signal intensity on images without magnetization transfer: MTR (M0 M1)/M0. The result was displayed as a color-coded map of the magnetization transfer ratio.

Ernst et al

MR Imaging
MR imaging was performed on a 1.5-T imager (GE Medical Systems; Milwaukee, Wis) equipped with the SR120 echoplanar imaging hardware. Conventional
regression analysis. A P value below.05 was considered statistically significant. All group averages were reported as the mean SD.

RESULTS

The dependence of the magnetization transfer ratio on the lesion type and lesion size is shown in Figure 1. There was no overlap in either the minimum or average magnetization transfer ratios. As a result, the difference in the two magnetization transfer ratio measures between the two groups was highly significant (P .0001 for both variables). However, minimum magnetization transfer ratios showed better separation between the groups than did the average magnetization transfer ratios (Fig 1). The average magnetization transfer ratio in PML lesions was 26.1% 4.0 and in HIV-WML 38.0% 2.6; the average minimum magnetization transfer ratios were 10.0% 5.9 and 29.1% 3.2, respectively. In comparison, the magnetization transfer ratio of normal-appearing white matter was 47.9% 2.2. The magnetization transfer ratio separated PML lesions from HIV-WML for even the smallest lesions studied. When the minimum or average magnetization transfer ratio for each PML lesion was plotted versus lesion age, no correlation was observed between the two variables. In contrast, the minimum but not the average magnetization transfer ratio of PML lesions was inversely related to the lesion size (r 0.41, P .04, Fig 1). One very large lesion with an area of 11.6 cm2 was excluded from this analysis; inclusion of this lesion improved the correlation (r 0.49, P .01). In the HIVWML group, the average but not the minimum magnetization transfer ratio correlated with the lesion size (r 0.51, P .03). Typical FLAIR images and magnetization transfer ratio maps in two patients with HIV-WML are shown in Figure 2. Both MR images showed a well-defined hyperintense white matter lesion in the centrum semiovale. There was no enhancement on the gadolinium-enhanced images. The magnetization transfer ratio in both lesions was mildly reduced. Figure 2 also shows a FLAIR image and a magnetization transfer ratio map of a large PML lesion in the left parietal white matter and of a smaller PML lesion in the right parietal white matter. The two lesions spared the gray matter and were hyperintense, similar to HIV-WML, on

Figure 2. Magnetization transfer ratio maps (left) and corresponding FLAIR images (right) of two HIV-WML (top and middle) and PML lesions (bottom). Despite similar appearances on the FLAIR images, the magnetization transfer ratios of the lesions (arrows) are markedly different. The HIV-WML show only moderate, and relatively homogeneous, reductions in magnetization transfer ratio, whereas the PML lesions exhibit areas of very low magnetization transfer ratio. This difference in the magnetization transfer ratio appearance is probably due to the fact that PML is a demyelinating disease, whereas myelin is relatively intact in HIV-WML. The same magnetization transfer ratio color scale is used for both lesions; bright yellow corresponds to the highest magnetization transfer ratio value of 52%.
To draw regions of interest, the magnetization transfer ratio maps were aligned (ie, shifted and scaled) on the computer with the anatomic images. Each lesion was manually outlined on the FLAIR images. If a lesion was visible on several sections, the region of interest was defined on the section that showed the most severe abnormalities in the magnetization transfer ratio. Because magnetization transfer ratio in the lesions was usually heterogeneous, the average and minimum values were determined for each lesion. The area of each region of

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interest (in square centimeters) was also recorded.

Statistical Analysis

Statistical analyses were performed (STATVIEW; Abacus, Berkeley, Calif). An unpaired Student t test was used to determine the statistical significance of differences between the magnetization transfer ratios in PML lesions and HIV-WML. The relationship between magnetization transfer ratio and lesion size or duration of PML was evaluated by means of linear
Progressive Leukoencephalopathy and White Matter Lesions in AIDS 541
the FLAIR images. There was no enhancement on the gadolinium-enhanced images. However, the magnetization transfer ratio in the larger lesion was markedly reduced, with an average magnetization transfer ratio of 21.7% (minimum, 3.4%); the average and minimum magnetization transfer ratios of the smaller lesion were 26.4% and 8.7%, respectively. These two lesions, similar to most other PML lesions studied, exhibited lowest magnetization transfer ratio in the center of the lesion, with a radial increase in the magnetization transfer ratio toward normal values.

DISCUSSION

Findings in our study demonstrate that considerable difference exists between the magnetization transfer characteristics of PML lesions and HIV-WML in patients with AIDS. PML lesions are characterized by very low magnetization transfer ratio values (mean, 26.1%), compared with that for normal white matter (mean, 47.9%). In contrast, HIV-WML show only moderate decreases in magnetization transfer ratio (mean, 38.0%). It is important to note that all HIV-WML in our study were well-defined hyperintense lesions in the centrum semiovale on T2weighted or FLAIR images (Fig 2). Consequently, magnetization transfer MR imaging may be useful for differentiating PML lesions from nondemyelinating hyperintense white matter abnormalities in patients with AIDS, even if both types of lesions have similar appearance on T2weighted MR images. This is important since not all PML lesions in patients with AIDS show typical radiologic features such as a subcortical white matter location and lack of enhancement after injection of contrast material (12,19,28). Atypical features, such as posterior fossa location, enhancement with gadolinium, atrophy, involvement of deep gray matter, and widespread punctate abnormalities, have been described by several authors (12,19,2225). In a recent MR study of 20 PML patients, we found that 50% had posterior fossa lesions, and 20% had lesions that enhanced with contrast material (25). In these atypical cases, the quantitative magnetization transfer ratio value might be used to support or refute a possible diagnosis of PML. The observed difference in the magnetization transfer ratio abnormalities between PML and HIV-WML most likely reflects differences in pathophysiology. PML is caused by infection of oligodendrocytes by the JC virus, which produces
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demyelinating lesions seen at neuropathologic examination and MR imaging (12,1521). In contrast, the histopathologic characteristics of HIV-associated brain injury include the presence of macrophages, microglia nodules, multinucleated giant cells, reactive astrogliosis, and perivascular lymphocytic infiltration. PML lesions are characterized by marked demyelination and marked magnetization transfer ratio decreases, whereas HIVWML are primarily nondemyelinating and exhibit only moderate magnetization transfer ratio reductions. This fact supports the concept that the high magnetization transfer ratio of normal white matter is facilitated by the presence of myelinated axons (14). Our results confirm those in previous reports of magnetization transfer studies in PML patients. In a group of HIVpositive patients with either PML or HIVWML, Dousset et al (29) observed a larger reduction in the magnetization transfer ratio of PML lesions (average magnetization transfer ratio 22%) compared with that of HIV-WML (average magnetization transfer ratio 40%). Gillams et al (30) also reported reduced magnetization transfer ratio in seven patients with HIV leukoencephalopathy; unfortunately, the investigators did not quantify magnetization transfer ratio, and they pooled patients with PML and HIV-WML. In a case report, Kasner et al (6) presented the case of a patient with PML, and found that the magnetization transfer ratio in the PML lesion was approximately 40% lower than that in normal white matter and that the reduced magnetization transfer ratio remained unchanged at 3 and 9 months after the initial presentation. In an atypical case of PML, Ng et al (7) also observed reduced magnetization transfer ratio in a PML lesion. In summary, findings in our study, in accordance with all prior observations, demonstrate that PML lesions show significantly greater reduction in magnetization transfer ratio than do HIVWML. The magnetization transfer ratio features of PML lesions appear similar to those of lesions in patients with multiple sclerosis, another demyelinating disease. In more than 200 multiple sclerosis plaques, Dousset et al (3) and Grossman (31) found an average magnetization transfer ratio of 62% compared with normal white matter (3,31). Tomiak et al (32) found that multiple sclerosis lesions aged less than 1 year had a significantly lower magnetization transfer ratio than older lesions (age, 1 year), and they concluded that the magnetization transfer

ratio might be potentially useful in determining the age of these lesions. In a study by Gass et al (5), the magnetization transfer ratio was inversely correlated with clinical disability. Taken together, these findings suggest that magnetization transfer MR imaging may be useful to subcategorize multiple sclerosis lesions and to follow up patients during drug treatment and may have prognostic value (31). In contrast, our findings in PML lesions studied cross-sectionally in time did not demonstrate a statistically significant correlation between magnetization transfer ratio and lesion age; this is mostly due to a relatively large variation in magnetization transfer ratio among new lesions (age, 2 months). This variation may be due to differences in the rate of disease progression among patients. For example, some of our patients experienced fulminant progression of PML with very low magnetization transfer ratio values within 12 months after disease onset, whereas disease in other patients progressed much more slowly and exhibited considerably lower magnetization transfer ratio decreases in the same time period. One of the current limitations of the use of the magnetization transfer ratio as an adjunct diagnostic test in white matter diseases in AIDS is that to our knowledge no data are available on the magnetization transfer ratio features of WML due to other diseases, such as viral infection due to cytomegalovirus, herpes simplex, or varicella zoster. However, since these viral infections generally do not cause extensive demyelination, as seen in PML, one would predict that the reduction in magnetization transfer ratio in these other viral lesions may be only moderate. Another potential pitfall of magnetization transfer MR imaging is that early PML lesions may exhibit only moderate decreases in the magnetization transfer ratio and thus appear similar to that of HIV-WML. However, there was no overlap between the magnetization transfer ratios of the 25 PML lesions and the 17 HIV-WML analyzed in our study. Therefore, the diagnostic accuracy of the magnetization transfer ratio in differentiating PML from HIV-WML appears to be well over 90%. Importantly, the separation between PML lesions and HIV-WML was maintained even in relatively small lesions with areas as small as 0.5 cm2. Thus, it appears that PML lesions cause severe reductions in the magnetization transfer ratio rapidly and that some of these lesions at early stages may be detected even when disease in the patients is asymptomatic. However, these issues will have to be
addressed in future longitudinal studies. Longitudinal studies also may be able to help resolve the important question whether there is a lower magnetization transfer ratio threshold that would indicate irreversible damage to the brain tissue. Findings in our study show significant differences in the magnetization transfer ratio abnormalities between PML lesions and HIV-WML. Therefore, magnetization transfer MR imaging is a noninvasive tool that may allow differentiation between PML and HIV-WML in patients with AIDS. Future longitudinal studies will be required to assess whether magnetization transfer MR imaging is also valuable for predicting disease progression and for monitoring therapy in patients with PML.

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