Hot cross bun sign in JC-Virus Granule cell neuronopathy in HIV infected patient - a case report.

BACKGROUND: John Cunningham virus related granule cell neuronopathy (JCV-GCN) is a rare manifestation of the reactivation of infection of the cerebellar granule cells by the JCV, mostly in immunocompromised individuals. The "hot cross bun" (HCB) sign is a cruciform hyperintensity seen in the midpons on T2-weighted and fluid attenuated inversion recovery (FLAIR) sequences on magnetic resonance imaging (MRI) of the brain. An index sub-Saharan Africa report of a case of JCV-GCN with HCB sign follows. CASE PRESENTATION: A 27-year-old HIV positive female with JCV-GCN was re-evaluated for chronic ataxia complicated by subacute progressive horizontal diplopia. Cerebrospinal fluid (CSF) had trace Mycobacterium tuberculosis (MTB) detected by GeneXpert Mycobacterium Tuberculosis/Rifampicin resistance (MTB/RIF) assay test. Brain MRI revealed diffuse severe cerebellar atrophy with a hot cross bun sign and patchy enhancement contiguous to the cerebellar dentate nuclei bilaterally. She continued Highly Active Antiretroviral Therapy (HAART) pending CSF HIV viral load counts and started standard brain TB local treatment regimen protocols with progressive improvement in limb ataxia. CONCLUSIONS: In conclusion, finding of the HCB sign may be indicative of and aid diagnosis of JCV-GCN in the right clinical context. This could be an important neuroimaging marker in this context, that may radiologically be more evident in later stages of the condition.

Electroencephalography as a diagnostic tool for late-onset efavirenz neurotoxicity syndrome.

INTRODUCTION: To examine electroencephalogram (EEG) as a diagnostic tool for late-onset efavirenz (EFV) neurotoxicity syndrome (LENS), an uncommon but severe and potentially fatal complication of EFV therapy. METHODS: We conducted a Retrospective case-control study. EEGs from confirmed cases of LENS (clinical syndrome and plasma EFV >4ug/mL) recorded from June 2016 to May 2021 were compared with control EEGs from the same time-period. Controls were adults (18-70 years) with a similar indication for EEG (eg. encephalopathy or confusion), dysrhythmia generalised grade II, and LENS excluded. EEGs were reviewed by two blinded interpreters given a description of the characteristic EEG changes, ie. persistent, diffuse, high voltage, bisynchronous, monomorphic 4-7 Hz theta frequency waveforms with transient attenuation on eye opening. Interpreters were asked to determine whether EEGs showed definite, probable or no changes. RESULTS: Thirteen LENS cases were compared with 50 control EEGs. Interpreter 1 labelled 11/13 LENS cases as having define or probable changes, and interpreter 2 labelled 10/13. Interpreter 1 labelled probable changes in 1/50 controls and interpreter 2 in 3/50. Neither interpreter labelled any controls as having definite changes. Interrater reliability was good with 95% agreement and a Cohen's kappa of 0.83. Sensitivity of EEG under these conditions for the diagnosis of LENS was 85% and 77% for interpreters 1 and 2 respectively, and specificity was 98% and 94%. CONCLUSIONS: EEG is a useful tool in the diagnosis of LENS which can be used to aid clinical decisions while awaiting EFV levels, or in low-resource settings where EFV levels are not available.

Different clinical phenotypes of AQP4-IgG positive NMOSD in two first degree relatives.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) are autoimmune inflammatory disorders of the CNS in which patients have severe relapses of optic neuritis and myelitis. Aquaporin-4 antibody (AQP4-IgG) positive NMOSD has not been reported in members of the same family in Sub Saharan Africa. We report the uncommon scenario in which both a Ugandan HIV positive woman and her HIV negative daughter were diagnosed with AQP4-IgG positive NMOSD. We discuss pathogenic mechanisms that may underlie familial presentation of AQP4-IgG positive NMOSD. CASE PRESENTATION: Case 1, a 54-year-old female teacher with a 20-year history of HIV infection and virally suppressed on Tenofovir, Lamivudine and Dolutegravir HAART regimen, presented with 8 months of progressive quadriparesis and urinary incontinence with a T6 sensory level. She had gadolinium enhancing longitudinally extensive transverse myelitis on MRI and was AQP4-IgG positive on serum studies. She received IV Methylprednisone 1 g daily for 3 days as a pulse and was continued on tapering doses of oral Prednisone with maintenance doses of Azathioprine. She showed slow improvements in limb motor function. Her daughter, case 2, is a 35-year-old HIV negative nutritionist, independently ambulant, with no known comorbidities or precedent autoimmune disease. She presented 1 year before her mother's AQP4-IgG positive NMOSD diagnosis with 7 months history of bilateral visual loss of rapid onset, with gadolinium-enhancing optic nerves on Brain and orbit MRI, in keeping with bilateral optic neuritis. She was AQP4-IgG positive on serum studies. She stabilized on tapered doses of oral Prednisone and continues daily oral Azathioprine with moderate improvement in her vision and no further relapses as yet. CONCLUSIONS: We add to existing literature and hypothesize that NMOSD appears to show a complex genetic background. To our knowledge, this is the first report in Sub-Saharan Africa, of familial AQP4-IgG positive NMOSD presenting with clinical heterogeneity between first degree relatives. A better understanding of the pathogenic mechanisms involved, including genome wide studies for particular risk loci for familial NMOSD, will be pivotal for future preventative and therapeutic strategies.

Breast diseases histologically diagnosed at a tertiary facility in Uganda (2005-2014).

BACKGROUND: The prevalence and distribution of histologically diagnosed breast disease are not well documented in low income countries, Uganda inclusive. Although the greater majority of breast lesions globally are benign, breast cancer is the most frequently diagnosed cancer all over the world. We aimed at documenting the prevalence of different breast diseases histologically diagnosed at the histopathology laboratory of the Department of Pathology of the Makerere University College of Health Sciences (MakCHS Lab) over a decade (2005-2014). We also describe the demographic characteristics of the patients in Uganda diagnosed with breast disease at the MakCHS Lab during the same period. METHODS: This was a 10 year retrospective study of histologically diagnosed breast disease between 2005 and 2014 inclusive at the MakCHS Lab. We extracted information from hard copies of all 2510 histopathology reports retrieved from archives of the Department of Pathology at the MakCHS Lab. 640 records that were either damaged beyond recognition of key details, were duplicated, were implausible or had no conclusive diagnosis made were excluded. Information to be analyzed was then entered into Epidata (version 3.1) on a password protected laptop. Data analysis was done using SPSS software (v16 for Windows × 64). RESULTS: From the 1870 patients' records eventually analyzed, breast disease was most diagnosed in female patients (97.1%). The overall mean age for breast disease diagnosis was 33 years (S.D ± 16.46) and median age 26 years (IQR: 20-43). Fibroadenoma (40.1%) was the most diagnosed breast disease overall. We noticed steadily increasing frequency of diagnosis of cancerous breast diseases over the last half of the study period. Invasive ductal carcinoma was the most diagnosed breast cancer (326 cases, 55.6%). A high female to male breast cancer ratio of 48:1 was observed. The highest regional breast cancer proportion was from the Western region of the Country. CONCLUSIONS: There is need for more research into the picture of breast disease in the country, covering various demographic characteristics of the country's population for all regions and informing about its incidence rates and prevalence and also the breast cancer risk estimate for benign breast disease.