Severe Neurological Presentation Research Articles

Pathognomonic neuroradiological signs in Wilson's disease – Truth or myth?

IntroductionWilson's disease (WD) is a treatable genetic disorder caused by impaired copper metabolism. Early diagnosis and correct anti-copper treatment are crucial for therapeutic success. Brain magnetic resonance imaging (MRI) is used both for diagnosis and treatment monitoring. Several neuroradiological signs have been proposed to be pathognomonic for WD; however, their frequency and significance are not established. The frequency and significance of these brain MRI signs were analyzed in a large cohort of WD patients. MethodsWe retrospectively analyzed 100 newly diagnosed, treatment-naive WD patients. Brain MRI was performed and the frequency of typical MRI changes was analyzed with demographic, clinical and laboratory characteristics of WD. ResultsPotentially pathognomonic brain MRI signs for WD occurred in 24% patients and in 43% (24/55) patients with neurological WD. Signs detected included the “face of the giant panda” in 15% of all patients (27.3% of neurological cases), “miniature panda” in 12% (21.8% of neurological cases), “split thalamus” in 7% (12.7% of neurological cases), and “bright claustrum” and “whorl” signs in 1 patients each. Signs were observed only in patients with neurological symptoms and were significantly associated with early age of onset/diagnosis, more severe neurological presentation and lower ceruloplasmin level (all p < 0.05). ConclusionsPotentially brain MRI pathognomonic signs occurred relatively rarely across all patients, most often in patients with early onset and severe neurological symptoms, and this knowledge may improve WD diagnosis. However, as these signs are also found in brain MRI in other disorders, they may not be truly pathognomonic of WD.

Neuromyelitis Optica spectrum disorders in the elderly

Introduction. Neuromyelitis Optica is a severe autoimmune inflammatory demyelinating disease that affects mainly the spinal cord and optic nerves with a young female predilection. It can present with a severe neurological presentation from the beginning with a poor prognosis. However, it is rare to see it in elderly subjects with aggressive and insidious onset of symptoms. Objective. Our cases highlight the varied clinical presentations of NMOSD and we believe that the diagnosis of NMOSD should be considered in elderly patients in the appropriate clinical setting despite the presence of unconventional symptoms.

Decline in mild stroke presentations and intravenous thrombolysis during the COVID-19 pandemic: The Society of Vascular and Interventional Neurology Multicenter Collaboration

BackgroundTo evaluate overall ischemic stroke volumes and rates, specific subtypes, and clinical presentation during the COVID-19 pandemic in a multicenter observational study from eight states across US. MethodsWe compared all ischemic strokes admitted between January 2019 and May 2020, grouped as; March-May 2020 (COVID-19 period) and March-May 2019 (seasonal pre-COVID-19 period). Primary outcome was stroke severity at admission measured by NIHSS stratified as mild (0−7), moderate [8–14], and severe (>14). Secondary outcomes were volume of large vessel occlusions (LVOs), stroke etiology, IV-tPA rates, and discharge disposition. ResultsOf the 7969 patients diagnosed with acute ischemic stroke during the study period, 933 (12 %) presented in the COVID-19 period while 1319 (17 %) presented in the seasonal pre-COVID-19 period. Significant decline was observed in the mean weekly volumes of newly diagnosed ischemic strokes (98 ± 3 vs 50 ± 20,p = 0.003), LVOs (16.5 ± 3.8 vs 8.3 ± 5.9,p = 0.008), and IV-tPA (10.9 ± 3.4 vs 5.3 ± 2.9,p = 0.0047), whereas the mean weekly proportion of LVOs (18 % ±5 vs 16 % ±7,p = 0.24) and IV-tPA (10.4 % ±4.5 vs. 9.9 % ±2.4,p = 0.66) remained the same, when compared to the seasonal pre-COVID-19 period. Additionally, an increased proportion of patients presented with a severe disease (NIHSS > 14) during the COVID-19 period (29.7 % vs 24.5 %,p < 0.025). The odds of being discharged to home were 26 % greater in the COVID-19 period when compared to seasonal pre-COVID-19 period (OR:1.26, 95 % CI:1.07–1.49,p = 0.016). ConclusionsDuring COVID-19 period there was a decrease in volume of newly diagnosed ischemic stroke cases and IV-tPA administration. Patients admitted to the hospital had severe neurological clinical presentation and were more likely to discharge home.

The Effect of Methylmalonic Acid Treatment on Human Neuronal Cell Coenzyme Q10 Status and Mitochondrial Function.

Methylmalonic acidemia is an inborn metabolic disease of propionate catabolism, biochemically characterized by accumulation of methylmalonic acid (MMA) to millimolar concentrations in tissues and body fluids. However, MMA’s role in the pathophysiology of the disorder and its status as a “toxic intermediate” is unclear, despite evidence for its ability to compromise antioxidant defenses and induce mitochondrial dysfunction. Coenzyme Q10 (CoQ10) is a prominent electron carrier in the mitochondrial respiratory chain (MRC) and a lipid-soluble antioxidant which has been reported to be deficient in patient-derived fibroblasts and renal tissue from an animal model of the disease. However, at present, it is uncertain which factors are responsible for inducing this CoQ10 deficiency or the effect of this deficit in CoQ10 status on mitochondrial function. Therefore, in this study, we investigated the potential of MMA, the principal metabolite that accumulates in methylmalonic acidemia, to induce a cellular CoQ10 deficiency. In view of the severe neurological presentation of patients with this condition, human neuroblastoma SH-SY5Y cells were used as a neuronal cell model for this investigation. Following treatment with pathological concentrations of MMA (>0.5 mM), we found a significant (p = 0.0087) ~75% reduction in neuronal cell CoQ10 status together with a significant (p = 0.0099) decrease in MRC complex II–III activity at higher concentrations (>2 mM). The deficits in neuronal CoQ10 status and MRC complex II–III activity were associated with a loss of cell viability. However, no significant impairment of mitochondrial membrane potential (ΔΨm) was detectable. These findings indicate the potential of pathological concentrations of MMA to induce a neuronal cell CoQ10 deficiency with an associated loss of MRC complex II–III activity. However, in the absence of an impairment of ΔΨm, the contribution this potential deficit in cellular CoQ10 status makes towards the disease pathophysiology methylmalonic acidemia has yet to be fully elucidated.

Emergency surgery for brainstem cavernoma haemorrhage with severe neurological presentation. Is it indicated and worthwhile?

Background: Brainstem Cavernoma (BSCM) haemorrhage is a complex condition, especially when patients present rapid neurological deterioration. Traditionally, these patients were initially treated by non-interventional means. Surgery was generally reserved for cases who presented a ‘benign’ evolution in a subacute/delayed fashion. Timing of surgery remains controversial. Since rebleeding is frequent and carries a high mortality, many of these patients do not tolerate this approach. Urgent/emergent surgery may be indicated and lifesaving.Methods: A single center experience is reported in which an aggressive approach was used with urgent/emergency surgery carried out on patients with BSCM haemorrhage and rapid neurological deterioration, ventilatory impairment and/or coma. A review of 5 consecutive cases where urgent/emergent surgery was performed is presented. The pre-operative status, pre- and post-operative examinations, surgical approach and neurological residual deficits/outcomes are reported.Results: Four females and one male with ages ranging from 36 to 66 years with rapid neurological deterioration, ventilatory impairment and/or coma were operated between 2011 and 2018. Favourable outcomes were observed with a modified Rankin Scale varying from 1 to 4. Cranial nerve deficits as well as motor and sensitive deficits were observed but all the patients recovered cognitive integrity.Conclusions: Our small series reveals an acceptable outcome with ultra-early surgery. This approach appears to be a valid option when there is rapid neurological deterioration, respiratory impairment and/or early onset coma. However, further studies are required to elucidate the optimal strategy.

Pediatric Hepatic Wilson's Disease: Experience From a Tertiary Care Center

Background and Aim: As there is paucity of exclusive literature on pediatric hepatic Wilson's disease (WD), this study was aimed to evaluate clinical presentation and outcome of children with hepatic WD. Methods: WD children satisfying ≥2 of 3 criteria (serum ceruloplasmin <20 mg/dL, positive Kayser-Fleischer ring, 24 h urine copper > 40 μg) ± liver histology managed in our department from January 2007 to June 2016 were analysed. Patients with ≥9 months of adequate follow-up were evaluated for response to chelation therapy. They were analysed as following categories: (a) complete improvement (asymptomatic + normalization of transaminases, serum albumin and coagulation); (b) partial improvement (asymptomatic + near normalization of transaminases + serum albumin or cogulation); (c) progression (deterioration of synthetic functions, decompensation or death); (d) drug toxicity Results: 111 WD children aged 108 (36–180) months had an overall PELD score 16 (−11 to 60). Liver histology was consistent with WD in 68% (n = 27/40). Figure 1 shows the presentation and outcome. Chelation was started in 84% (n = 94). 14% (n = 16) patients died in hospital due to advanced disease. 66 with follow up of 43 (9–144) months were analysed for outcome. 92% (n = 60) were on D-penicillamine monotherapy and 6% (n = 4) with additional severe neurological presentation were on D-penicillamine and zinc. Among those on D-penicillamine monotherapy, favourable outcome was seen in 58% (n = 35). 13% (n = 8) had drug toxicity and 12% (n = 7) required addition of zinc due to disease progression. 6% (n = 4) were started on trientine. Overall favourable outcome was observed in 70% (n = 46). Conclusions: This is the first and largest pediatric experience of hepatic WD. Majority of the hepatic WD can be managed on D-penicillamine monotherapy. Addition or change of chelation is required in select situations of drug toxicity and neurological presentation The authors have none to declare.

Cervical neurenteric cyst and Klippel-Feil syndrome: An abrupt onset of myelopathic signs in a young patient

Abstract Neurenteric cysts (NECs), also called enterogenous cysts or enterogenic cysts, are congenital malformative anomalies of endodermal origin that manifest with a variety of disorders, including spine anomalies. Neurenteric cysts are uncommon developmental disorders reported in 0.7%–1.3% of all spinal tumors. Klippel-Feil syndrome (KFS) defines a malformative spine disorder presenting with congenital fusion of cervical vertebrae and/or other parts of the spine. In patients with KFS, NECs are rarely reported; they may be silent for long periods of time, showing a slow progressive course or manifesting with an acute, severe neurological presentation or with fluctuating myelopathic symptoms. We report a young patient affected by KFS associated with a NEC which, in a short period of time, progressively caused myelopathic symptomatology. Surgical intervention resulted in resolution of the neurological signs.

Abstract TP315: Predictors of Thrombolysis Administration in Patients with Minor Stroke or TIA in the Florida Puerto Rico Collaboration to Reduce Stroke Disparities (FL-PR CReSD) Study

Background: Minor stroke/TIA is the most common cause for thrombolysis exclusion in patients acutely presenting to the hospital. Thrombolysis administration in this subgroup is highly variable amongst different clinicians and institutions. We aim to study the predictors of thrombolysis in patients with mild ischemic stroke in the FL-PR CReSD Study. Methods: 73,712 patients with ischemic stroke/TIA were prospectively enrolled from January 2010 to April 2015. We included 7,746 patients who had persistent neurological symptoms with NIHSS score ≤5 and arrived within 4 hours of symptom onset. Multilevel logistic regression analysis was used to identify independent predictors of thrombolysis in the subgroup of patients without contraindications to thrombolysis Results: 6,826 patients (25% final diagnosis TIA, 75% minor stroke) were included (mean age=70±14 years), 52.7% male, 70.3% white, 13% black, 16.7% Hispanic, median NIHSS=2 (IQR=1,4). Patients who received thrombolysis (N=1281, 18.7%) were younger (67 vs. 70.7 years, P&lt;0.001), had less vascular risk factors (HTN, DM, dyslipidemia), lower risk of prior vascular disease (MI, PVD, previous stroke) and had a higher presenting median NIHSS score (4 vs. 2, P&lt;0.0001). In the multivariable analysis, younger age (OR 1.02, 95% CI 1.02-1.03, P&lt;0.0001), white or Hispanic vs. black (OR 1.2, 95% CI 1.04-1.37, P=0.0097), early hospital arrival (unit change in 30 min.) (OR 1.26, 95% CI 1.21-1.31, P&lt;0.0001), arrival by EMS (OR 1.28, 95% CI 1.08-1.49, P&lt;0.0001), higher NIHSS score (OR 1.96, 95% CI 1.87-2.06, P&lt;0.0001), altered level of consciousness (OR 1.43, 95% CI 1.11-1.85, P=0.0062) and aphasia at presentation (OR 1.34, 95% CI 1.13-1.58, P=0.0008) were independent predictors of thrombolysis administration. Conclusion: Minor acutely presenting stroke patients were more likely to receive thrombolysis if they were young, white or Hispanic, and arrived early to the hospital with more severe neurological presentation specifically aphasia and altered level of consciousness. Identification of predictors of thrombolysis utilization is important in the design of educational programs and randomized trials to increase the use of thrombolysis for minor stroke.

A novel mutation inCYP24A1gene in an infant with severe hypercalcemia and unique neurological presentation

A novel mutation in<i>CYP24A1</i>gene in an infant with severe hypercalcemia and unique neurological presentation

Cerebral malaria in children : an update

Cerebral malaria (CM) is the most severe neurological presentation of acute falciparum malaria. It is a medical emergency, the hallmark of which is the presence of coma probably due to diffuse encephalopathy. A compromised microcirculation with sequestration of parasitized erythrocytes is central to the pathogenesis of cerebral malaria. The death is unacceptably high even with effective antimalarials in tertiary care hospital. The mainstay of treatment of cerebral malaria include prompt diagnosis and early institution of effective antimalarial therapy, recognition of complications, and appropriate supportive management in an ICU. Neurological sequlae are increasingly recognized, but further research on the pathogenesis of coma and neurological damage is required to develop other ancillary treatmentsNorthern International Medical College Journal Vol.6(2) 2015: 45-47

Central pontine and extrapontine myelinolysis: a systematic review.

The purpose was to perform a systematic review of studies on central pontine and extrapontine myelinolysis [forms of osmotic demyelination syndrome (ODS)] and define the spectrum of causes, risk factors, clinical and radiological presentations, and functional outcomes of this disorder. A thorough search of the literature was conducted using multiple databases (PubMed, Ovid Medline and Google) and bibliographies of key articles to identify all case series of adult patients with ODS published from 1959 to January 2013. Only series with five or more cases published in English were considered. Of the 2602 articles identified, 38 case series were included comprising a total of 541 patients who fulfilled our inclusion criteria. The most common predisposing factor was hyponatremia (78%) and the most common presentation was encephalopathy (39%). Favorable recovery occurred in 51.9% of patients and death in 24.8%. Liver transplant patients with ODS had a combined rate of death and disability of 77.4%, compared with 44.7% in those without liver transplantation (P<0.001). ODS is found to have a good recovery in more than half of cases and its mortality has decreased with each passing decade. Favorable prognosis is possible in patients of ODS, even with severe neurological presentation. Further research is required to confirm the differences found in liver transplant recipients.

A pediatric case of gluten sensitivity with severe neurological presentation

Neurologic manifestations are present in a reasonable proportion of adult celiac patients and can be the first sign of gluten sensitivity. In children, the risk of neurological complications is lower, and gluten sensitivity with neurological presentation seems to be rare. We report a case of gluten sensitivity with severe neurological presentation in a 3-year-old girl. In the absence of gastrointestinal symptoms, the presence of white matter lesions in cerebral magnetic resonance imaging suggested an acute disseminated encephalomyelitis. Recurrence of neurologic symptoms and cerebral lesions over a long period of time made the authors consider an autoimmune/inflammatory systemic disease. IgA anti-transglutaminase (TG) 2 was elevated and duodenal biopsy confirmed the presence of enteropathy. A gluten-free diet led to complete resolution of neurological manifestations and arrest of white matter lesions progression. In children with unclear neurologic manifestations with probable autoimmune etiology, anti-TG2 autoantibody titers should be determined considering the possibility of gluten sensitivity. Gluten-free diet remains the only effective treatment reported to date and, therefore, should be recommended to all patients with gluten sensitivity despite the type of manifestations. More studies, focusing on neurological manifestations and its response to gluten-free diet, are needed.

Pediatric perimedullary arteriovenous fistula of the conus medullaris supplied by the artery of Desproges-Gotteron

The cone artery, or artery of Desproges-Gotteron, is sometimes seen arising from the internal iliac artery. The authors describe a case of a symptomatic perimedullary arteriovenous fistula (AVF) of the conus medullaris in an 8-year-old boy who presented with a protracted history of urinary difficulty and severe sudden-onset right lumbosciatic pain that evolved to severe paraparesis with compromise of the sphincter muscles. The spinal AVF, which was supplied by the cone artery and a thoracic radiculomedullary artery that joined at the fistula site in a large partially thrombosed varix, was completely occluded with Onyx liquid embolic. The patient's clinical condition improved rapidly after embolization. As shown in this patient, urgent endovascular embolization of spinal AVFs can be very rewarding, even in patients with severe neurological presentation. The artery of Desproges-Gotteron appears to be a rare arterial variation. To the authors' knowledge, this is the first pediatric case of a conal AVF supplied by this artery.

Ataxia‐telangiectasia: Mild neurological presentation despite null ATM mutation and severe cellular phenotype

Ataxia-telangiectasia (A-T) is an autosomal recessive disorder characterized by progressive neurodegeneration, immunodeficiency, susceptibility to cancer, genomic instability, and sensitivity to ionizing radiation. A-T is caused by mutations that eliminate or inactivate the nuclear protein kinase ATM, the chief activator of the cellular response to double strand breaks (DSBs) in the DNA. Mild A-T is usually caused by ATM mutations that leave residual amounts of active ATM. We studied two siblings with mild A-T, as defined by clinical examination and a quantitative A-T neurological index. Surprisingly, no ATM was detected in the patients' cells, and sequence analysis revealed that they were homozygous for a truncating ATM mutation (5653delA) that is expected to lead to the classical, severe neurological presentation. Moreover, the cellular phenotype of these patients was indistinguishable from that of classical A-T: all the tested parameters of the DSB response were severely defective as in typical A-T. This analysis shows that the severity of the neurological component of A-T is determined not only by ATM mutations but also by other influences yet to be found.