Sarcoidosis with basal ganglial infiltration presenting as Parkinsonism

BACKGROUND

The differential diagnosis of Parkinsonism may, at times, be very challenging. With the exception of drug-induced and “vascular” aetiologies, most other causes may be easily missed. This is particularly important for causes that may respond to medical intervention. Careful evaluation of the personal, familial and environmental context, mode of onset and progression, clinical features and drug response, together with imaging, biochemical and molecular tests, help in determining the underlying disease and may increase chances of successful medical interventions. Here, we report a case of progressive Parkinsonism of unusual aetiology.

CASE PRESENTATION

A 58-year-old woman presented in June 2006 complaining of fatigue, slow and monotonous speech, left foot dragging and micrographia that gradually developed over a period of 12 months. Her symptoms resulted in significant deterioration of her social and professional life. She had a 10-month history of untreated, asymptomatic sarcoidosis diagnosed by routine biopsy of an enlarged left supraclavicular lymph node. Neurological examination revealed Parkinsonism (bradykinesia and rigidity) with slow alternating movements and finger tapping (left>right), mild left hemiparesis (deltoids 4/5, elbow flexors, elbow extensors and wrist dorsiflexors 4+/5, finger abductors 4/5 and hand grip 4+/5) and left Babinski sign. Bradykinesia was predominantly of extrapyramidal type without evidence of clinically significant pyramidal slowing and weakness during rapid alternating movements.

INVESTIGATIONS

Serological tests for antibodies to syphilis and viruses (hepatitis B virus (HBV), herpes simplex virus (HSV), John Cunningham virus (JCV), HIV varicella, measles) were negative. Blood tests for endocrine/metabolic abnormalities were positive for dyslipidaemia and hyperthyroidism. Anti-nuclear antibody, tumour markers and heavy metals screening was negative. Serum paraneoplastic antibodies were absent. Cerebrospinal fluid (CSF) was normal. Concentrations of angiotensin converting enzyme were not raised in the serum or the CSF. Brain MRI showed right basal ganglia, external capsule and medial temporal lobe areas of haemorrhage with perilesional fast fluid-attenuated inversion-recovery (FLAIR) abnormality extending into the anteriomedial temporal lobe (fig 1A). There was abnormal EEG activity with bursts of proximal theta activity, originating from the left temporal region. Flow cytometry was negative. Right stereotactic frame-based brain parenchymal biopsy of the lesion site revealed reactive CNS tissue with perivascular chronic inflammation and non-caseating granulomas (fig 1B) consistent with definite neurosarcoidosis. Special stains were negative for fungus and acid fast organisms.

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Figure 1

A. Axial fast fluid-attenuated inversion-recovery (FLAIR) imaging showing right basal ganglia, external capsule and medial temporal lobe areas of haemorrhage and surrounding perilesional abnormality extending into the anteriomedial temporal lobe. B. Brain tissue biopsy (H&E staining) of the right basal ganglia showing reactive central nervous system (CNS) tissue with perivascular chronic inflammation and non-caseating granulomas (arrowheads) consistent with definite neurosarcoidosis. C. Follow-up MRI 12 months after initial evaluation showing increased bilateral T1W signal in the basal ganglia. D. 18F-FDG positron emission tomography (PET) imaging showing hypometabolism of globus pallidus and caudate heads (right>left).

DIFFERENTIAL DIAGNOSIS

Idiopathic Parkinson disease.

Other idiopathic Parkinsonian syndromes (progressive supranuclear palsy, multiple system atrophy).

Secondary Parkinsonism (tardive, vascular).

TREATMENT

The patient was started on a high dose of prednisone (60 mg/day) with very good initial response. Over the next 2 months she was able to resume some activities of daily living with mild residual weakness and mild bilateral Parkinsonism. Reduction of prednisone due to mild side effects resulted in symptom worsening.

OUTCOME AND FOLLOW-UP

Symptoms mildly progressed and within the next 12 months the patient also developed masked facies, mild left lower limb spasticity and wide-based, unsteady shuffling gait with turning difficulties. She started complaining of urinary urgency that progressed to episodes of incontinence (about 1/day) and depressive symptomatology. At that time, the dose of azathioprine was 50 mg three times a day and prednisone 100 mg every other day. Her treatment also included tolterodine tartrate for her overactive bladder and prophylactic phenytoin with satisfactory control of her symptoms. A follow-up MRI revealed bilateral basal ganglia involvement, which was previously seen only in the right putamen (fig 1C). 18F-FDG positron emission tomography (PET) imaging showed hypometabolism of the globus pallidus and caudate heads (fig 1D). Although structural lesions are usually associated with hemi-Parkinsonism, more rarely, as in this case, they can affect both sides simultaneously giving bilateral symptoms. The patient’s neurological status has been stable without progression of her Parkinsonian symptomatology.

DISCUSSION

Sarcoidosis is a granulomatous multisystem disorder of unknown cause. It can affect any part of the nervous system in about 5% to 15% of patients.1^,2 Neurosarcoidosis can appear in an acute explosive fashion or as a slow, chronic illness. Cranial nerves, the hypothalamus and the pituitary gland are most commonly involved.3 Hypoknetic extrapyramidal symptoms responsive to immunmodulating therapy have been very rarely reported in the context of neurosarcoidosis.4 Here, we report for the first time brain parenchymal biopsy-confirmed bilateral basal ganglia infiltration mimicking a Parkinsonian syndrome.