Neurology Clinicopathological Case

Clinicopathological case A 63 year old right handed accountant was referred to neurology in early 2014 with unsteadiness and somnolence. He had become unwell in summer 2013, with a knot-like sensation in his abdomen, which settled with omeprazole, and daytime somnolence (Epworth 15). He had struggled increasingly with work, resulting in withdrawing from two major contracts. When seen in the neurology clinic he reported unsteadiness and 2 stone weight loss. He thought he had poor spatial awareness, and had accidentally crossed between lanes on the motorway; at his wife’s suggestion he had stopped driving. He had become withdrawn, lost enjoyment playing his guitar, had reduced libido, and was reluctant to leave the house. He had been fit and well until these symptoms. He was taking omeprazole and fluoxetine. He left school aged 18 years, and studied accountancy. He had been successful in his work. He had right mastoid surgery in 1969 and 1983, since then had been prone to ear discharge. He lived with his wife and 21 year old daughter. He had never smoked and drank little alcohol. He had completed a 400 mile sponsored bike trip in India in 2011. His mother had developed dementia towards the end of life and died aged 85. His maternal grandmother had also demented. His initial examination showed a broad based unsteady gait, minimal finger-nose ataxia, worse on the left. His eye movements were normal except for square wave jerks. He was not parkinsonian and his ACE(R) was 99/100. He was subsequently diagnosed with obstructive sleep apnoea and initially responded well to CPAP but by mid 2015 he was sleeping up to 20 hours a day. His gait became impaired and he started using a stick. He developed generalised itch, wearing gloves at night to prevent drawing blood. He became increasingly apathetic, his wife would return home from work to find him still in pyjamas, he spent hours doing nothing. He made inappropriate jokes, and needed help resolving his mother in law’s financial affairs after she died. He developed anxiety, a fear of falling, and experienced shaking episodes related to this. He had difficulty using the TV remote. He developed urinary hesitancy and erectile dysfunction. He was investigated for reflux symptoms and loose stools (see results). On examination in July 2015 he had bilateral palmomental reflexes, snout and pout reflexes, jerky saccades with nystagmus. His speech was slurred. There was no bradykinesia, but he had a staring appearance. Tone and power were normal. His gait was broad based. He had difficulty with praxis and sequencing. Plantars were flexor and tendon reflexes normal. His investigations were unremarkable, except for a lumbar puncture showing 7 white cells and unmatched oligoclonal bands in the CSF (see results). He received a trial of prednisolone 40 mg/day for one month, then reduced over 2 weeks, without benefit. By March 2016 he was using a wheelchair. He had memory problems, and was performing poorly in TV quizzes, which he had previously enjoyed. He was rude and hurtful to family members and strangers. His ACE(R) was 69/100 (attention 16/18, memory 16/26, fluency 3/14, language 23/26, visuospatial 7/16). He had hypomimia, increased tone thoughout, prominent cerebellar signs with broken pursuit and nystagmus and past pointing. In April 2016 he was admitted to hospital after a fall, and treated for a urinary tract infection. He was discharged to a nursing home, where he became increasingly unwell, and was bed bound by October 2016 with a poor swallow. He died on November 3rd 2016 aged 65. Bloods ● ● ● ● ● ● ● ● FBC, ESR, glucose, LFTs, TFTs. Urea, electrolytes and creatinine, and CK all normal Vitamin E 5.3umol/mmol (within normal limits) Serum lipids and TGs unremarkable Antibodies to VGKC,VGCC,GAD, IA2, NMDA, TPO, AchR, Yo, Hu and Ri, tTG IgA all negative Extractable nuclear antigens, ANA, CCP negative HIV and Anti-treponemal IgG negative Ataxia genetics: SCA1, 2, 3, 6, 7, FRDA and FXTA all negative Neurodegenerative gene panel: C9Orf72 5-10 repeats (normal) both alleles, APP, CHMP2B, FUS, GRN, LRRK2, MAPT, PARK2, PSEN1, PSEN2, SOD1, SQSTM1, TARDBP, UBQLN2, VAPB, VCP sequences all normal. CSF ● March 2014: WCC 6; RCC 0; glucose CSF 3.3 (serum 4.1), protein 0.31g/L; multiple unpaired IgG OCBs in CSF. ● Sept 2015: WCC 7; RCC 0; glucose CSF 3.7 (serum 4.5), protein 0.33g/L; multiple unpaired OCBs in CSF; tau 111, beta-amyloid 104 (normal), Whipples PCR negative; CSF microscopy no organisms seen; Enterovirus, HSV1 PCR, HSV2 PCR, Parechovirus PCR, VZV PCR all negative; CSF cytology (4mL) no significant cellular component, no evidence of malignancy or inflammation. Imaging ● March 2014: MR head - Generalised atrophy, advanced for age, no other abnormalities ● Jan 2015: MRI head (unenhanced). Moderate global cerebral atrophy, advanced for age, unchanged from 2014. Mild chronic microvascular changes also accelerated for age. No other abnormalities. T1 T2 CSF suppressed June 2014: DaTSCAN– Normal ● Sept 2015: CT CAP with contrast: Unremarkable EEG 2015: Bursts of generalised slow with some intermixed sharp waves; in keeping with cerebral dysfunction but not specific. Sleep study: May 2014: 55 apnoeas/hypopnoeas per hour Colonoscopy – Two polyps removed from proximal ascending colon: tubular adenoma showing low grade dysplasia. Pedunculated polyp in splenic flexure: tubular adenoma, no sign of invasion. Two biopsies of right and left colon: normal. Upper GI endoscopy – prepyloric biopsies: chemical gastritis; D2 biopsies: mild duodenitis