Progressive multifocal leukoencephalopathy secondary to idiopathic CD4 lymphocytopenia treated with pembrolizumab.

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease due to a lytic infection of oligodendrocytes caused by John Cunningham polyoma virus (JCV) infection. Idiopathic CD4+ T-cell lymphocytopenia (ICL) is a very rare cause of PML. METHODS: We present an individual with PML secondary to ICL treated with 3 doses of pembrolizumab, a Programmed-Death-1 Immune Checkpoint Inhibitor following with complete resolution of symptoms and conduct a review of the literature. CONCLUSION: This report illustrates the objective clinical and radiological improvement in a patient with PML due to ICL and suggests further study of immune checkpoint inhibitors as potential treatment for patients with PML.

Anomalies in the review process and interpretation of the evidence in the NICE guideline for chronic fatigue syndrome and myalgic encephalomyelitis.

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a disabling long-term condition of unknown cause. The National Institute for Health and Care Excellence (NICE) published a guideline in 2021 that highlighted the seriousness of the condition, but also recommended that graded exercise therapy (GET) should not be used and cognitive-behavioural therapy should only be used to manage symptoms and reduce distress, not to aid recovery. This U-turn in recommendations from the previous 2007 guideline is controversial.We suggest that the controversy stems from anomalies in both processing and interpretation of the evidence by the NICE committee. The committee: (1) created a new definition of CFS/ME, which 'downgraded' the certainty of trial evidence; (2) omitted data from standard trial end points used to assess efficacy; (3) discounted trial data when assessing treatment harm in favour of lower quality surveys and qualitative studies; (4) minimised the importance of fatigue as an outcome; (5) did not use accepted practices to synthesise trial evidence adequately using GRADE (Grading of Recommendations, Assessment, Development and Evaluations trial evidence); (6) interpreted GET as mandating fixed increments of change when trials defined it as collaborative, negotiated and symptom dependent; (7) deviated from NICE recommendations of rehabilitation for related conditions, such as chronic primary pain and (8) recommended an energy management approach in the absence of supportive research evidence.We conclude that the dissonance between this and the previous guideline was the result of deviating from usual scientific standards of the NICE process. The consequences of this are that patients may be denied helpful treatments and therefore risk persistent ill health and disability.

IgG4-related hypertrophic pachymeningitis with chronic subdural haematoma.

Hypertrophic pachymeningitis is a rare disorder of the dura mater of the spine or brain. It can be caused by inflammatory, infective or neoplastic conditions or can be idiopathic. We report a man with hypertrophic pachymeningitis and bilateral chronic subdural haematoma caused by IgG4-related disease. We highlight the diagnostic challenges and discuss possible underlying mechanisms of subdural haematoma formation in inflammatory conditions. Isolated IgG4-related hypertrophic pachymeningitis with chronic subdural haematoma is very rare; previously reported cases have suggested a possible predilection for men in their sixth decade, presenting with headache as the dominant symptom. Given the rarity and complexity of the condition, it should be managed in a multidisciplinary team setting.

HTLV-1 encephalitis.

A 53-year-old woman developed subacute onset of upper limb weakness, sensory loss and cerebellar dysfunction. She was known to have human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy. MR scan of the brain showed extensive T2 hyperintensity within the deep and subcortical white matter, with punctate contrast enhancement. Cerebrospinal fluid (CSF) was lymphocytic with very high levels of HTLV-1 provirus in both CSF and peripheral blood lymphocytes. We diagnosed HTLV-1 encephalomyelitis and started high-dose methylprednisolone followed by a slow corticosteroid taper. She recovered well and regained functional independence in the upper limbs. Neurological manifestations of HTLV-1 infection extend beyond classical 'tropical spastic paraparesis' and are under-recognised. We review the literature on HTLV-1 encephalitis and discuss its diagnosis and management.

Catatonia with GABAA receptor antibodies.

A 22-year-old African woman developed acute behavioural change, against a background of sickle cell disease with strokes requiring a ventriculoperitoneal shunt. She alternated between mutism with prolonged staring and posturing, and a state of agitation with elation and echolalia. Cerebrospinal fluid (CSF) protein was elevated and electroencephalogram showed mild slowing with bitemporal slow and sharp waves. We suspected catatonia secondary to possible autoimmune encephalitis but her condition persisted despite intravenous methylprednisolone. After identifying a positive serum anti-gamma-aminobutyric acid-A (GABAA) antibody, treatment with intravenous immunoglobulin, oral corticosteroids and rituximab led to gradual improvement. Patients with catatonia may show reduced GABAA receptor density and there are two other reports of catatonia with anti-GABAA antibodies. This patient's treatment response supports the antibody's causative role.