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Metachromatic leukodystrophy diagnosed after traumatic brain injury: a case report/ Travmatik beyin hasan sonrasi farkedilen metakromatik lokodistrofi: bir olgu sunumu.


Metachromatic leukodystrophy (MLD) is a rare inherited neurodegenerative disorder caused by a deficiency of a lysosomal enzyme arylsulphatase A. Herein, we report the case of a patient with late-onset MLD who presented with symptoms inconsistent with traumatic brain injury. The diagnosis of MLD was based only on MRI findings and low levels of arylsulphatase A. Although there was an underlying serious neurodegenerative disorder, the patient responded well to rehabilitation.

Key Words: Metachromatic leukodystrophy, brain plasticity, traumatic brain injury, electrophysiologic studies, rehabilitation, MRI


Metakromatik lokodistrofi (MLD), lizozomal enzim arilsulfataz A eksikligi sonucu olusan nadir rastlanan herediter norodejeneratif bir bozukluktur. Biz bu yazimizda, travmatik beyin hasari semptomlarina uymayan, gec baslangicli bir MLD vakasi sunduk. Fakat tanisi sadece MR bulgulari ve dusuk arilsulfataz A duzeylerine dayanarak konuldu. Altta yatan bu kadar ciddi norodejeneratif bozukluk olmasina ragmen hasta rehabilitasyona cok iyi bir yanit verdi.

Anahtar Kelimeler: Metakromatik lokodistrofi, beyin plastisitesi, travmatik beyin hasari, elektrofizyolojik calismalar, rehabilitasyon, MR goruntuleme


Metachromatic leukodystrophy (MLD) is a rare inherited neurodegenerative lysosomal disease caused by deficient activity of arylsulphatase A (1). Late-onset forms are the least common of all MLD's (2). The deficiency of arylsulphatase A leads to storage of cerebroside sulphate in the neural tissues. The disease is characterized by demyelination, affecting mainly the central and peripheral nervous systems (3). In late-onset MLD, psychotic disorders and dementia usually precede the onset of the neurological symptoms (4). Cases of late-onset MLD are rare and they have not been studied extensively as far as symptomatology and neuroimaging are concerned (1).

This article presents a late-onset MLD case diagnosed incidentally after a severe traumatic brain injury. The patient demonstrated significant functional recovery in spite of the presence of neurodegenerative concurrent disease.

Case Report

A 37-year-old woman was admitted to Baskent University, Yapracik Rehabilitation Unit for rehabilitation after traumatic brain injury. Her medical history revealed that she had been experiencing seizures approximately three times every five years since she was 17, which were left untreated. Otherwise, she was normal. Six months before admission, the patient had sustained a head injury from a brick fallen from the third floor. She had experienced posttraumatic amnesia for three days. This injury was so severe that she had to stay in the intensive care unit for six months and later she was referred for rehabilitation. On admission, neurological examination revealed intact vision and normal eye movements. She could not talk due to the tracheostomy, so that her Mini-Mental State Examination (MMSE) score could not be determined at baseline. Her speech was mildly dysarthric after removal of tracheostomy. Global muscle strength of her upper extremities was 0/5 and of the lower extremities was 2/5 according to the Medical Research Council scale (5). Tonus in the upper extremities was flask, although there was a mild increase in the tonus of her lower extremities. In her lower extremities, deep tendon reflexes were absent and plantar responses remained unmoved bilaterally. She had no sitting balance and could not turn in bed independently. Her sensation was intact.

Magnetic resonance imaging (MRI) of the brain and cervical spinal cord demonstrated increased intensity on FLAIR and T2-weighted images of bilateral periventricular and superficial white matter, posterior limb of capsula interna and corpus callosum (Figure 1, 2, 3, 4). These areas were hypointense on T1-weighted images and contrast enhancement was not observed following intravenous paramagnetic contrast administration. Cervical spine MRI demonstrated increased intensity within the spine on T2-weighted images without paramagnetic contrast enhancement on post-contrast T1-weighted images. The presence of diffuse demyelination raised the question of an existing neurodegenerative disorder, particularly MLD. The blood levels of vitamin B12 and folate were within normal ranges. To rule out infectious etiologies, serum viral markers were studied. The patient was negative for both cytomegalovirus and Epstein-Barr virus IgM antibodies. Immunoglobulin M and IgG antibodies for herpes simplex virus type I and type II were negative. The cerebrospinal fluid (CSF) examination did not reveal any microorganisms and the cultures failed to demonstrate any of the microorganisms as well, but the protein concentration was elevated (73.9 mg/dl) (normal range: 15-45 mg/dl). Oligoclonal band was not observed in CSF protein electrophoresis. Serum level of arylsulphatase A was close to the lower limit (53 nmol/mg) (normal range: 50-990 nmol/mg). Metachromatic granules were absent in the urine. Urine and plasma amino acids were reported as normal.


Nerve conduction studies were performed to both lower extremities and to the right upper extremity. Conduction velocities in motor nerves (bilateral tibial and common peroneal nerves) were found lower than the normal values. The amplitudes of compound muscle action potentials were reduced in the left common peroneal, right tibial, right median and ulnar nerves. Conduction block was not observed. Sensory nerve action potential amplitudes and conduction velocities were within normal limits. Somatosensory evoked potentials were not elicited.




At discharge after a 50-day rehabilitation period, she was able to walk in parallel bars with minimal support. MMSE score was 22 at discharge. Upper and lower extremity strength has increased up to 3/5. Follow-up examination one year after the head injury revealed continuous functional improvement. She has nearly returned back to her baseline functional status. Final MMSE score was 24.


We report here the case of a patient with late-onset MLD who presented with symptoms inconsistent with head injury. The diagnosis was established with MRI findings and low levels of arylsulphatase A. Evidence of peripheral neuropathy as demonstrated by electrophysiological studies and elevated CSF protein levels, further supported the diagnosis. Despite the unfortunate combination of traumatic brain injury and MLD in this patient, she demonstrated significant recovery after rehabilitation efforts and long-term follow-up. Review of the literature did not give any information about neuroplasticity after head injury in the presence of a neurodegenerative disease such as MLD.

Uniform slowing of nerve conduction velocities is the neurophysiological hallmark of MLD and other inherited demyelinating polyneuropathies (6). In previously reported cases of MLD, various electromyographic findings have been reported ranging from severe demyelinating neuropathy (7) to solely mildly prolonged distal motor latency in the tibial nerve within the context of normal conduction velocities (4). In some cases of MLD, no clinical or neurophysiological sign of peripheral neuropathy could be demonstrated (8,9). In our case, decreased motor nerve conduction velocities in the lower extremities were observed.

Epilepsy tends to be a late feature of the adult MLD (4). On the other hand, in previous studies, some cases with epilepsy as an early manifestation of late-onset MLD have been presented (1,4). Our case supported the observation that epileptic seizures can be the only clinical presentation of late-onset MLD. There is no description of the type of seizures in the adult form of the disease (1).

Epileptic seizures were the presenting feature of this late-onset MLD and MLD possibly did not have a negative effect on brain plasticity.

DOI: 10.4274/tffr.94824


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(2.) Coulter-Mackie MB, Applegarth DA, Toone JR, Cagnier L, Anzarut AR, Hendson G. Isolated peripheral neuropathy in atypical metachromatic leukodystrophy: a recurrent mutation. Can J Neurol Sci 2002;29:159-63.

(3.) Kazibutowska Z, Bal A, Gotba A, tugowska A. Metachromatic leukodystrophy in adult patient initially diagnosed as multiple sclerosis. Neurol Neurochir Pol 2002;36:1209-19.

(4.) Cengiz N, Ozbenli T, Onar M, Yildiz L, Ertas B. Adult metachromatic leukodystrophy: three cases with normal nerve conduction velocities in a family. Acta Neurol Scand 2002;105:454-7.

(5.) John J. Grading of muscle power: comparison of MRC and analogue scales by physiotherapists. Medical Research Council. Int J Rehabil Res 1984;7:173-81.

(6.) Cameron CL, Kang PB, Burns TM, Darras BT, Jones HR Jr. Multifocal slowing of nerve conduction in metachromatic leukodystrophy. Muscle Nerve 2004;29:531-6.

(7.) Comabella M, Waye JS, Raguer N, Eng B, Dominguez C, Navarro C, et al. Late-onset metachromatic leukodystrophy clinically presenting as isolated peripheral neuropathy: compound heterozygosity for the IVS2+1G[R]A mutation and a newly identified missense mutation (Thr408lle) in a Spanish family. Ann Neurol 2001;50:108-12.

(8.) Gallo S, Randi D, Bertelli M, Salviati A, Pandolfo M. Late onset MLD with normal nerve conduction associated with two novel missense mutations in the ASA gene. J Neurol Neurosurg Psychiatry 2004;75:655-7.

(9.) Giordana MT, Piccinini M, Palmucci L, Buccinna B, Ramondetti C, Brusco A, et al. Myelin-associated glycoprotein is altered in a familial late-onset orthochromatic leukodystrophy. Brain Pathol 2005;15:116-23.

Selcuk GUZEL, Ayce ATALAY *, Nur TURHAN **, Ulku Sibel BENLI **, Huseyin Gurkan TORE **

Agri State Hospital, Department of Physical Medicine and Rehabilitation, Agri, Turkey

* Acibadem University, School of Medicine, Department of Physical Medicine and Rehabilitation, Istanbul, Turkey

** Baskent University Faculty of Medicine, Department of Physical Medicine and Rehabilitation, Ankara, Turkey

Address for Correspondence:/Yazisma Adresi: Selcuk Guzel MD, Agri State Hospital, Department of Physical Medicine and Rehabilitation, Agri, Turkey Phone: +90 506 328 47 79 E-mail:

Received/Gelis Tarihi: March/Mart 2010 Accepted/Kabul Tarihi: July/Temmuz 2011
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Title Annotation:Case Report/Olgu Sunumu
Author:Guzel, Selcuk; Atalay, Ayce; Turhan, Nur; Benli, Ulku Sibel; Tore, Huseyin Gurkan
Publication:Turkish Journal of Physical Medicine and Rehabilitation
Date:Sep 1, 2011
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