Severe NAD(P)HX Dehydratase (NAXD) Neurometabolic Syndrome May Present in Adulthood after Mild Head Trauma.

We have previously reported that pathogenic variants in a key metabolite repair enzyme NAXD cause a lethal neurodegenerative condition triggered by episodes of fever in young children. However, the clinical and genetic spectrum of NAXD deficiency is broadening as our understanding of the disease expands and as more cases are identified. Here, we report the oldest known individual succumbing to NAXD-related neurometabolic crisis, at 32 years of age. The clinical deterioration and demise of this individual were likely triggered by mild head trauma. This patient had a novel homozygous NAXD variant [NM_001242882.1:c.441+3A>G:p.?] that induces the mis-splicing of the majority of NAXD transcripts, leaving only trace levels of canonically spliced NAXD mRNA, and protein levels below the detection threshold by proteomic analysis. Accumulation of damaged NADH, the substrate of NAXD, could be detected in the fibroblasts of the patient. In agreement with prior anecdotal reports in paediatric patients, niacin-based treatment also partly alleviated some clinical symptoms in this adult patient. The present study extends our understanding of NAXD deficiency by uncovering shared mitochondrial proteomic signatures between the adult and our previously reported paediatric NAXD cases, with reduced levels of respiratory complexes I and IV as well as the mitoribosome, and the upregulation of mitochondrial apoptotic pathways. Importantly, we highlight that head trauma in adults, in addition to paediatric fever or illness, may precipitate neurometabolic crises associated with pathogenic NAXD variants.

Incidentally Identified Pulmonary AVM: An Unusual Cause for Stroke in a Young Patient.

Pulmonary arteriovenous malformation is an uncommon though important potential source for embolic right-to-left extracardiac shunt as a cause for both silent and clinically evident stroke. We present this case to highlight this pathology as a cause for stroke, the importance of treating this malformation, even if incidentally identified, and finally the role of echocardiography in screening for extracardiac shunt and indicating those patients that may benefit from further investigations looking for extracardiac shunt.

Nontraumatic spinal cord ischaemic syndrome.

This study presents the clinical features and functional outcomes of eight consecutive patients who were admitted to our institution between 2012 and 2014 with nontraumatic spinal cord infarction (SCI), a rare and devastating condition. We also present a literature review of aetiologies and prognostic factors relevant to our case series. The mean age of our cohort was 64 years and five patients were female. Aortic disease was causative in three, including one patient with biopsy confirmed giant cell arteritis. Fibrocartilaginous embolism was a possible aetiology in two others, anterior spinal artery aneurysm in one, and the cause was undetermined in two patients. American Spinal Injury Association impairment scale (ASIA) scores at nadir (time of maximum severity of signs) were B in three, C in three and D in two patients (all were wheelchair dependent). At last follow-up, ASIA scores were C in one, D in five and E in one patient. One patient died, two remained wheelchair dependent, four required a walking aid or frame and one was mobilising independently. A literature review of 11 patient series of nontraumatic SCI found that prognosis is primarily determined by the severity of motor or sensory involvement, in particular, initial and nadir ASIA A/B scores which strongly correlate with poor outcome. In the majority of series, 40-60% of patients had initial ASIA A/B scores with a similar proportion remaining wheelchair dependent on follow-up. Most patients in our cohort had nadir ASIA C/D scores, which may explain their better outcomes.

Acute dysphasia and reversible cognitive decline in a patient with probable cerebral amyloid angiopathy-related inflammation.

Cerebral amyloid angiopathy related inflammation (CAAri) is becoming increasingly recognised as a subset of cerebral amyloid angiopathy (CAA). CAAri generally presents with subacute cognitive decline, headaches, seizures, behavioral changes, and focal neurological deficits. We describe a patient who developed acute dysphasia and reversible cognitive decline due to probable CAAri. CT brain showed bilateral vasogenic edema in the cerebral hemispheres, predominantly involving the parietal and temporal lobes, left greater than right without enhancement. Magnetic resonance brain imaging showed extensive multifocal areas of subcortical white matter T2 hyperintensity in the frontal and temporal regions with associated mass effect, negligible enhancement, and multiple foci of microhemorrhage on susceptibility weighted imaging sequences consistent with a diagnosis of probable CAAri. She responded dramatically to a course of intravenous methylprednisolone followed by further immunosuppression with pulse intravenous cyclophosphamide. Her dysphasia resolved within 5 days of intravenous methylprednisolone therapy. Her MMSE improved from 11/30 at day 5 of admission to 28/30 at 6-month follow-up. The notable features of our case were the unusual CT findings, which were inconsistent with stroke and diagnostic utility of susceptibility-weighted magnetic resonance imaging in confirming the diagnosis which allowed for prompt institution of immunosuppression.

Abdominal wall haematoma in the obese: a dangerous phenomenon.

We report the case of a 59-year-old obese female who developed an abdominal wall haematoma during administration of prophylactic clexane. Compared with the non-obese, the subcutaneous tissue of the obese is considered dysfunctional and has a different vascular structure and extra-cellular matrix composition. While the development of an abdominal wall haematoma is relatively uncommon, when they occur they can have fatal consequences. The altered subcutaneous tissue environment in the obese attenuates the normal external compression of an abdominal wall haematoma and as a result the obese are at greater risk of haemorrhage.