Aggressive Kaposi's Sarcoma in a 6-month-old African infant: Case Report and Review of the Literature.

Kaposi's sarcoma (KS), known to exist in Africa for a century now, was rare in children and unknown in the newborn. With the onset of the HIV/AIDS epidemic, a more aggressive, disseminated type of KS (AKS) was recognized. Recently KS was diagnosed in a 6-month-old infant in Tanzania. Data support the notion that HHSV8 infectivity can be potentiated with HIV infection and thus produce multiple lesions in different anatomical sites early in life. Furthermore, the available evidence would suggest a nonsexual route of HHSV8 infection, possibly from mother to fetus

Dramatic clinical response to ultra-high dose IVIg in otherwise treatment resistant inflammatory neuropathies

Background Intravenous immunoglobulin (IVIg) has short and long-term efficacy in both chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy with conduction block (MMNCB). There is potential for under and over-treatment if trial regimens are strictly adhered to in clinical practice where titrating dose to clinical response is recommended. Methods We report the response to high-dose IVIg (>2 g/kg/6 weeks) in a subgroup of patients with definite CIDP or MMNCB who were unresponsive to ‘usual’ dosing. IVIg frequency and dosing was determined for each individual by subjective and objective outcome measures for impairment, grip strength, and activity and participation. Results Six patients (three with chronic inflammatory demyelinating polyneuropathy (CIDP), three with MMN) were included. Two patients (one CIDP and one MMNCB) returned to full-time work on fractionated IVIg doses of 5 g/kg/month and 9 g/kg/month. Patient three (CIDP) failed numerous other immunosuppressants but responded to short-term fractionated 4 g/kg/month of IVIg. Patient four has severe, refractory, childhood-onset CIDP, remains stable but dependent currently on 6.9 g/kg/month of IVIg. Patients five and six, both with MMNCB, required short term 4.5–5 g/kg/month to recover significant bilateral hand strength. No IVIg-related adverse events occurred in any individual. Conclusions These six cases demonstrate the safety and effectiveness of a treatment approach that includes individualised but evidence-based clinical assessment and, when necessary, high-doses of IVIg to restore patients’ strength and ability to participate in activities of daily activities. Careful patient selection is important

Delayed diagnosis of neuroschistosomiasis in a non-endemic country: A tertiary referral centre experience

BACKGROUND: Neuroschistosomiasis is a severe complication of schistosomiasis, triggered by the local immune reaction to egg deposition, with spinal cord involvement the most well recognised form. Early treatment with praziquantel and high dose steroids leads to a reduction of neurological sequelae. The rarity of this condition in returning travellers to high income countries can result in delayed diagnosis and treatment. We aimed to evaluate the diagnosis and management of neuroschistosomiasis in a UK national referral centre. MATERIALS AND METHODS: A retrospective review of confirmed clinical cases of spinal schistosomiasis referred to the Hospital for Tropical Diseases, UK, between January 2016 and January 2020 was undertaken. Electronic referral records were interrogated and patient demographic, clinical, laboratory, and radiological data collected. RESULTS: Four cases of neuroschistosomiasis were identified. The median age at diagnosis was 28 (range 21 to 50) with three male patients. All patients had epidemiological risk factors for schistosomiasis based on travel history and freshwater exposure; two in Uganda (River Nile), one in Malawi and one in Nigeria. All patients presented with features of transverse myelitis including back pain, leg weakness, paraesthesia and urinary dysfunction. The mean time from presentation to health services to definitive treatment was 42.5 days (range 16–74 days). Diagnosis was confirmed with CSF serology for schistosomiasis in all cases. Radiological features on MRI spine included enhancement focused predominantly in the lower thoracic spinal cord in three cases and the conus in one patient. All patients received a minimum of three days of oral praziquantel and high dose steroids. At three-month follow-up, one patient had complete resolution of symptoms and three had residual deficit; one patient was left with urinary and faecal incontinence, another had urinary retention, and the final patient has persistent leg pains and constipation. CONCLUSION: We observed a marked delay in diagnosis of neuroschistosomiasis in a non-endemic country. We advocate undertaking a thorough travel history, early use of imaging and CSF schistosomal serology to ensure early diagnosis of neuroschistosomiasis in patients presenting with consistent symptoms. If schistosomal diagnostics are not immediately available, presumptive treatment under the guidance of a tropical medicine specialist should be considered to minimize the risk of residual disability. We advocate for consensus guidelines to be produced and reporting to be performed in a uniform way for patients with spinal schistosomiasis

HIV and the brain: from AIDS to old age

The field of HIV medicine has changed rapidly in the last two decades since effective and tolerable antiretroviral treatment became available. As a result, although classical opportunistic infections of the brain have become less common, clinicians need to be aware of a wider range of acute and chronic complications of HIV and its treatment. In this article, we summarise major opportunistic infections, immune reconstitution inflammatory syndrome, HIV-associated neurocognitive disorders, and cerebrovascular disease in HIV positive patients. We also emphasise the preventability and reversibility of most of the central nervous system complications of HIV, and hence the importance of early diagnosis of HIV and involvement of clinicians with special expertise in HIV medicine

Pilot phenotype and natural history study of hereditary neuropathies caused by mutations in the HSPB1 gene

Mutations in HSPB1 are one of the commonest causes of distal Hereditary Motor Neuropathy (dHMN). Transgenic mouse models of the disease have identified HDAC6 inhibitors as promising treatments for the condition paving the way for human trials. A detailed phenotype and natural history study of HSPB1 neuropathy is therefore required in order to inform the duration and outcome measures of any future trials. Clinical and neurophysiological data and lower limb muscle MRI were collected both prospectively and retrospectively from patients with mutations in HSPB1. The natural history was assessed by recording the weighted Charcot-Marie-Tooth Examination Score (CMTES) at annual intervals in a subset of patients. 20 patients from 14 families were recruited into the study. The average age of onset was in the 4th decade. Patients presented with a length dependent neuropathy but with early ankle plantar flexion weakness. Neurophysiology confirmed a motor neuropathy but also showed sensory nerve involvement in most patients. Cross sectional muscle MRI revealed soleus and medial gastrocnemius fat infiltration as an early signature of mutant HSPB1 disease. In this study neither semi quantitative muscle MRI, the CMTES nor neurophysiology were able to detect disease progression in HSPB1 neuropathy over 1 or 2 years. Further studies are therefore required to identify a suitable biomarker before clinical trials in HSPB1 neuropathy can be undertaken

Acetylcholinesterase inhibition ameliorates deficits in motivational drive

<p>Abstract</p> <p>Background</p> <p>Apathy is frequently observed in numerous neurological disorders, including Alzheimer's and Parkinson's, as well as neuropsychiatric disorders including schizophrenia. Apathy is defined as a lack of motivation characterized by diminished goal-oriented behavior and self-initiated activity. This study evaluated a chronic restraint stress (CRS) protocol in modeling apathetic behavior, and determined whether administration of an anticholinesterase had utility in attenuating CRS-induced phenotypes.</p> <p>Methods</p> <p>We assessed behavior as well as regional neuronal activity patterns using FosB immunohistochemistry after exposure to CRS for 6 h/d for a minimum of 21 d. Based on our FosB findings and recent clinical trials, we administered an anticholinesterase to evaluate attenuation of CRS-induced phenotypes.</p> <p>Results</p> <p>CRS resulted in behaviors that reflect motivational loss and diminished emotional responsiveness. CRS-exposed mice showed differences in FosB accumulation, including changes in the cholinergic basal forebrain system. Facilitating cholinergic signaling ameliorated CRS-induced deficits in initiation and motivational drive and rescued immediate early gene activation in the medial septum and nucleus accumbens.</p> <p>Conclusions</p> <p>Some CRS protocols may be useful for studying deficits in motivation and apathetic behavior. Amelioration of CRS-induced behaviors with an anticholinesterase supports a role for the cholinergic system in remediation of deficits in motivational drive.</p

Can compressive thoracic cord lesions cause a pure lower motor neurone syndrome?

Compressive lesions of the spinal cord usually cause a syndrome of upper motor neurone weakness, spasticity and sensory loss below the level of the lesion. It has long been recognised that compressive cervical cord lesions may present as isolated lower motor neurone weakness of the upper limbs, a syndrome termed cervical spondylotic amyotrophy. We describe two patients presenting with isolated lower motor neurone weakness of the lower limbs in association with a compressive cord lesion at T11/12, a condition we have termed thoracic spondylotic amyotrophy

The benefits of 24/7 in-house intensivist coverage for prolonged-stay cardiac surgery patients

ObjectiveThe objective of our study was to evaluate the efficacy of 24/7 in-house intensivist care for patients requiring prolonged intensive care unit (ICU) stay following cardiac surgery.MethodsA propensity-matched retrospective before-and-after observational study comparing 2 models of ICU physician staffing was undertaken. Previously, residents (with intensivist backup) provided care for patients after cardiac surgery (surgical ICU cohort). ICU physician staffing was modified with the implementation of 24/7 in-house board-certified intensivist coverage in a cardiac surgery ICU (cardiac surgery ICU cohort) for postoperative care. Patients with a prolonged ICU stay (ie, >48 hours) were identified and their outcomes analyzed for both models of care.ResultsPropensity matching between cohorts was successful for 271 patients (75.7%), with matched patients being used for comparison. There was no difference in ICU or 30-day mortality. There was also no difference in ICU length of stay (LOS); however, the median hospital LOS was significantly shorter in the cardiac surgery ICU cohort (12.3 vs 11.0 days; P < .01). There was a decrease in the proportion of patients receiving transfused red blood cells in the cardiac surgery ICU cohort (80.8% vs 65.7%; P < .001). The cardiac surgery ICU cohort had reduced complications relating to sepsis (4.7% vs 0.7%; P < .01) and renal failure (22.5% vs 12.5%; P < .01); however, the identification of neurologic dysfunction was significantly higher (11.1% vs 20.7%; P < .01).ConclusionsFor patients requiring a prolonged ICU stay, our model of 24/7 in-house intensivist coverage was not associated with changes in ICU LOS, nor ICU and 30-day mortality. However a reduction in blood product use, ICU complications, and total hospital LOS was observed

The Queen Square Encephalitis Multidisciplinary Team Meeting - experience over three years, pre and post the COVID-19 pandemic

Background: Patients with suspected encephalitis continue to represent a diagnostic and therapeutic challenge, even in highly resourced centres. In February 2018, we set up a monthly in-person multidisciplinary team meeting (MDT). We describe the experience and outcomes of the MDT over three years. Methods: A retrospective analysis was performed to summarise patient demographics, MDT outcomes and final diagnoses. Results: Over the three-year period, 324 discussions of 238 patients took place. Cases were diverse; approximately 40% related to COVID-19 or brain infection, 40% autoimmune or other inflammatory disorders and 20% encephalitis mimics or uncertain aetiologies. Feedback from an online survey sent to referring teams and attendees highlighted the value of the MDT; 94% reported the discussion was useful and 69% reported resulting change in patient management. Conclusions: Multidisciplinary input is crucial in this challenging area, ensuring that all diagnostic avenues are explored and opening doors to novel diagnostics and therapeutics. It also supports clinicians dealing with unwell patients, including in centres where less specialist input is available, and when decisions have to be made where there is little or no evidence base

Evaluation of a locked nucleic acid form of antisense oligo targeting HIF-1α in advanced hepatocellular carcinoma

BACKGROUND: Hypoxia-inducible factor 1α (HIF-1α) is a gene that regulates tumor survival, neovascularization and invasion. Overexpression of HIF-1α correlates with poor prognosis in hepatocellular carcinoma (HCC). RO7070179 is a HIF-1α inhibitor that decreases HIF-1α mRNA and its downstream targets, it could be a potential treatment in HCC. AIM: To evaluate safety and preliminary activity of RO7070179 in patients with previously treated HCC, with focus on a patient with prolonged response to RO7070179. METHODS: In the preclinical study of RO7070179 in a HCC xenograft model, the mice were separated into 4 groups with each group received doses of 0, 3, 10 and 30 mg/kg for total 10 doses. HCC patients who failed at least one line of systemic treatment, received RO7070179 as a weekly infusion, each cycle is 6 wk. We evaluated the safety and HIF-1α mRNA levels of RO7070179. RESULTS: Preclinical evaluation of RO7070179 in orthotopic HCC xenograft model showed no significant differences in HCC tumor weight between the 3 and 10 mg/kg groups. However, dose of 10 mg/kg of RO7070179, has shown 76% reduction of the amount of HIF-1α mRNA in HCC tissue. In the phase 1b study of RO7070179 in previously treated HCC patients, 8 out of 9 were evaluable: 1 achieved PR and 1 SD. The patient with PR responded after 2 cycles treatments, which has been maintained for 12 cycles. This patient also showed reduction in perfusion of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) after 1 cycle of treatment. After 1 cycle of treatment, both patients with PR and SD showed decrease in HIF-1α mRNA at the root of biopsies (each biopsy was divided into 2 specimens, the tip and the root). CONCLUSION: RO7070179 can reduce HIF-1α mRNA level in HCC patients with SD or PR. It is well tolerated at 10 mg/kg, with transaminitis as the dose of increased toxicity. This study indicates that RO7070179 might benefit HCC patients, and an early signal for clinical benefit can potentially be predicted through changes in either mRNA level or DCE-MRI within 1 cycle of therapy