Progressive multifocal leucoencephalopathy presenting with Parkinsonism

Sirs: Progressive multifocal leucoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by the JC virus strain of the papovavirus family [4]. JC virus infection is common in childhood and persists throughout life in latent form, affecting up to 80 % of adults. Reactivation of the virus occurs most often in the setting of impaired cell-mediated immunity although rare cases of primary PML have been described [3]. PML was originally described as a complication of chronic lymphocytic leukaemia and Hodgkin’s lymphoma [1]. The incidence of the condition has increased greatly in recent times as it is a frequent complication of AIDS [2]. Although patients with PML may show pathological involvement of the basal ganglia at autopsy, movement disorders are exceedingly rare as presenting symptoms. We describe the clinical, radiological and pathological features in a 78-year-old woman with chronic lymphocytic leukaemia (CLL) in whom PML presented with Parkinsonism. A 78-year-old right-handed woman, admitted for treatment of lower-limb cellulitis, complained of a two-month history of progressively worsening bilateral, asymmetric upper-limb tremor. This was predominantly a resting tremor. Her mobility had lessened in the preceding months. Chronic lymphocytic leukaemia (CLL) had been diagnosed seven years previously but specific treatment was not given. Several squamous cell carcinomas had been excised from her limbs in the past decade. She was a lifelong heavy smoker and required bronchodilator inhalers for chronic obstructive pulmonary disease but took no other medications. There was no history of use of neuroleptic medications. On examination there was bradykinesia with reduced facial expression and monotonous speech. She scored 21/30 on a MMSE, performed poorly on tests of attention and calculation and could recall only one of four objects at five minutes. Eye movements were normal. There was cogwheel rigidity and resting tremor affecting both upper limbs, more marked on the right.An element of action tremor was also present bilaterally. Limb power, reflexes and sensation were normal. Plantar responses were flexor.Walking was slowed but limited by pain due to lower limb cellulitis.A diagnosis of Parkinson’s disease was made. Treatment with low dose levodopa and selegiline was commenced and arrangements were made for outpatient cranial CT and neurology review. Seven weeks later there was evidence of deteriorating mobility and increasing withdrawal. On examination, there was evidence of a significant deterioration. She was poorly communicative and had a mild expressive dysphasia. There was prominent echolalia. Right hemi-inattention was noted. She was markedly dyspraxic. Once again, asymmetric upper limb rigidity and resting tremor were noted. Over the following weeks a progressive right hemiparesis developed. The right plantar response became extensor. Progressively worsening dementia followed and she became obtunded. She died 4 months after initial presentation. Routine blood investigations were normal apart from mild peripheral lymphocytosis. Cranial CT showed extensive hypodense lesions without mass effect within the deep white matter. Multiple, asymmetric high-signal abnormalities in the white matter were seen on T2-weighted and FLAIR cranial MRI (Figs. 1a and b). These lesions were hypointense on T1-weighted MRI and there was no contrast enhancement. No mass effect was seen. Routine cerebrospinal fluid analysis was normal and in particular, JC virus DNA was not detected in CSF by polymerase chain reaction (PCR). At necropsy, multiple foci of mottled yellow discoloration were seen involving the interface between grey and white matter in the frontal and parietal lobes on both sides. Lesions affecting the left striatum and thalamus and both cerebellar hemispheres were also noted. The substantia nigra and brainstem were unremarkable. No Lewy bodies were noted. Histological staining showed abundant demyelinating lesions in the grey and white matter. The lesions consisted of confluent regions of myelin loss with a scant perivascular infiltrate including numerous reactive astrocytes, myelin debris-filled macrophages and oligodendrocytes with nuclear inclusions (Fig. 2 a). The papova JC virus genome was detected using in-situ hybridisation techniques (Fig. 2 b). Elsewhere, nodal and splenic involvement by CLL was noted. We report the case of a 77-yearold woman with CLL in whom PML presented in an unusual fashion with a parkinsonian syndrome manifesting as bradykinesia, asymmetric upper-limb resting tremor and rigidity. In PML, virus-induced LETTER TO THE EDITORS