Case presentation:
A 61-year-old right-handed male, non-smoker, with no known past medical history, presented to the emergency department with five months history of progressive episodic unprovoked dysarthria of 10-15 seconds that occurred up to 30-40x day with intact awareness and comprehension. No specific aggravating factors and episodes do not exhibit diurnal variability. No history of preceding illness, trauma, and no constitutional symptoms were present. A review of systems revealed no extra-neurological manifestations, no mouth, genital ulcers, or blurred vision. No relevant family history, namely PDA, cerebellar ataxia, stammering, or stuttering.
Initial vitals were within normal parameters, temperature of 36 °C, respiratory rate of 19 breaths per minute, blood pressure of 120/62mmHg, oxygen saturation of 98%, and weight of 75 kg. His neurological examination was significant only for right dysmetria, dysdiadokokinesia, and inability to tandem. During the consultation, episodes were witnessed of 10-20 seconds stereotyped ataxic dysarthria with dysprosody and none unintelligible, pointing towards paroxysmal ataxia and dysarthria (PAD). Neuropsychological assessment was unrevealing, with normal Mini-Mental State Examination (MMSE) 29/30.
Initial workup; MRI head with contrast, showed 5 x 8 x 6 mm homogenously enhancing midbrain lesion a midline lesion with suspicious thickening and increased enhancement of left third cranial nerve, that raised the suspicion of underlying neoplastic vs. inflammatory etiology, such as lymphoma, glial tumors, or neuro-sarcoidosis or neuro-Bechet’s disease (Figure 1 A-D). Subsequent, full-body positron emission tomography (PET) and skeletal survey scan only showed a midline midbrain lesion with relative hypermetabolism otherwise unrevealing, excluding malignancy or other inflammatory processes. PET scan. Three months follow-up MRI head showed regression of the lesion (Figure 2 A-D), indicative of likely inflammatory process, and less likely glioma and metastasis, considering the interval minimal regression in size.
Lumbar puncture was performed, showed no pleocytosis, normal cerebrospinal fluid (CSF) biochemistry, culture for bacteria, and nPCR assays for a broad panel of viruses were negative. No malignant cells visible on cytology, and flow cytometry was not done due to paucity of cells, and no oligoclonal bands were detected. Blood tests were within normal parameters, including autoimmune workup and angiotensin converting enzyme level (ACE) 61 U/L (16-85 is normal reference range).
Despite the possible differential of glial tumor or lymphoma, a brain biopsy was deferred and not advised by the Neurosurgery team due to high risk. Due to anatomical location and radiological features, a possible diagnosis of neuro-Bechet’s was considered. The ophthalmology examination was normal, with no evidence of anterior or posterior uveitis on slit-lamp examination. Further HLA B-51 (Allele 2) analysis was requested (usually takes 3-4 weeks).
The patient was started on pulsed steroids with one gram of intravenous methylprednisolone for five days with a tapered dose (IVMP), which did not note any significant improvement in the frequency of his paroxysmal ataxia and dysarthria episodes. He was started on 200mg Carbamazepine and discharged home with regular follow-ups in the General Neurology clinic.
On four weeks follow-up, the patient developed fever, deranged liver function test (LFT), and severe skin maculopapular rash on more than one-third surface area, suggestive of Anti-convulsant Hypersensitivity Syndrome (AHS), significant enough to discontinue Carbamazepine and was switched to Baclofen. His PDA episodes were not adequately under control; hence a trial of Lacosamide 50mg BID controlled his PDA episodes.
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On five weeks follow up, HLA B-51 results reported positive, raising the diagnosis of PAD in neuro-Behcet’s with atypical radiological and clinical findings. Per Behcet’s syndrome Japanese Ministry of health and welfare criteria, our patient has one minor criterion due to a symptomatic central nervous system (CNS) lesion. A three-month follow-up MRI head showed slight interval regression in the midline midbrai1n lesion size to 4 x 7 x 5 mm in maximum AP, with decreased perilesional edema (Figure 2 A-B).