Clinical and genetic factors affecting diagnostic timeline of amyotrophic lateral sclerosis: a 15-year retrospective study.

OBJECTIVES: Amyotrophic Lateral Sclerosis (ALS) diagnosis can take 10-16 months from symptom onset, leading to delays in treatment and patient counselling. We studied the impact of clinical and genetic risk factors on the diagnostic timeline of ALS. METHODS: Baseline characteristics, family history, gene testing, onset location, time from symptom onset to diagnosis, and time from first doctor visit to suspected ALS was collected. We used multiple regression to assess the interaction of these factors on ALS diagnostic timeline. We analysed a subgroup of patients with genetic testing and compared positive or negative tests, sporadic or familial and ALS-related genes to time for diagnosis. RESULTS: Four hundred and forty-eight patients diagnosed with ALS at the University of Massachusetts Chan Medical Center between January 2007 and December 2021 were analysed. The median time to ALS diagnosis was 12 months and remained unchanged from 2007 to 2021 (p = 0.20). Diagnosis was delayed in patients with sporadic compared with familial ALS (mean months [standard deviation], 16.5[13.5] and 11.2[8.5], p < 0.001); cognitive onset (41[21.26]) had longer time to diagnosis than bulbar (11.9[8.2]), limb (15.9[13.2]), respiratory (19.7[13.9]) and ALS with multiple onset locations (20.77[15.71], p < 0.001). One hundred and thirty-four patients had gene testing and 32 tested positive (23.8%). Gene testing (p = 0.23), a positive genetic test (p = 0.16), different ALS genes (p = 0.25) and sporadic (p = 0.92) or familial (p = 0.85) ALS testing positive for ALS genes did not influence time to diagnosis. DISCUSSION: Time for ALS diagnosis remained unchanged from 2007 to 2021, bulbar-onset and familial ALS made for faster diagnosis.

Breast cancer-associated paraneoplastic neuromyelitis optica with cervical cord compression and spondylosis requiring laminectomy: A case report.

Neuromyelitis optica, an autoimmune inflammatory disorder affecting the central nervous system, can occur in a paraneoplastic context, although rare. We report an intriguing case of a 71-year-old woman with a history of triple-negative infiltrating ductal breast carcinoma, manifesting with paraneoplastic neuromyelitis optica that led to significant respiratory failure and required a cervical laminectomy. The patient presented with pain in the left breast, weakness in the lower extremities, and neck pain. The neurological evaluation showed 2/5 muscle strength in all extremities, diffuse hyperreflexia, and loss of multimodal sensation below the shoulder. She developed acute respiratory failure that required mechanical ventilation. Magnetic resonance imaging highlighted a diffuse abnormal increase in T2 signal intensity throughout the posterior and central portion of the cervical and thoracic spinal cord consistent with longitudinally extensive transverse myelitis, and significant cervical cord compression at C3-C4. Magnetic resonance imaging of the brain showed non-enhancing T2/fluid-attenuated inversion recovery (FLAIR) white matter hyperintensities and cerebellar hemispheres. The serum cell-based assay study demonstrated a high anti-aquaporin-4 immunoglobulin G titer (>1:160) confirming the diagnosis of neuromyelitis optica. She was taken for bilateral laminectomy from C3 to C6. Despite intravenous methylprednisolone and plasmapheresis treatment, no significant recovery was achieved, necessitating tracheostomy and percutaneous endoscopic gastrostomy. Subsequent rituximab treatment led to a mild improvement, with no new lesions on repeat magnetic resonance imaging. This case raises suspicion of the potential for neuromyelitis optica to occur as a paraneoplastic phenomenon, strengthening the need for vigilance in patients with malignancies.

A single-center retrospective study of hospitalized COVID-19 patients: demographics, laboratory markers, neurological complications, ICU admission, and mortality.

The coronavirus disease 2019 (COVID-19) pandemic has unveiled a wide array of clinical biomarkers, and neurological manifestations in affected patients, necessitating further exploration. Methods: This single-center retrospective study evaluated clinical and neurological sequelae, demographics, as well as laboratory markers, in hospitalized COVID-19 patients from January to September 2020. Results: Among 1248 inpatients (median age: 68 years; 651 women), 387 (31%) were admitted to the ICU. Central nervous system (CNS) manifestations were present in 521 (41.74%) patients, while peripheral nervous system manifestations were observed in 84 (6.73%). COVID-19-related mortality occurred in 314 (25.16%) cases. ICU-admitted patients were predominantly male (P<0.0001), older (age≥60; P=0.037) and had more comorbidities such as diabetes (P=0.001), hyperlipidemia (P=0.043), and coronary artery disease (P=0.015). ICU patients exhibited more CNS manifestations (P=0.001), including impaired consciousness (P<0.0001) and acute cerebrovascular disease (P=0.023). Biomarkers linked to admission to the ICU included elevated white blood cell count, ferritin, lactate dehydrogenase, creatine kinase, blood urea nitrogen, creatinine, and acute phase reactants (e.g. erythrocyte sedimentation rate and C-reactive protein). ICU patients demonstrated lower lymphocyte and platelet counts compared to non-ICU patients. Those with CNS involvement in the ICU often exhibited elevated blood urea nitrogen, creatinine, and creatine kinase levels. Higher mortality from COVID-19 was observed in ICU patients (P<0.0001). Conclusions: Multiple serum biomarkers, comorbidities, and neurological manifestations in COVID-19 patients have been consistently documented and may be linked to increased morbidity, ICU admission, and mortality. Recognizing and addressing these clinical and laboratory markers is essential for effective COVID-19 management.

Outcomes of Telestroke Inter-Hospital Transfers Among Intervention and Non-Intervention Patients.

Background: Telestroke is an established telemedicine method of delivering emergency stroke care. However, not all neurological patients utilizing telestroke service require emergency interventions or transfer to a comprehensive stroke center. To develop an understanding of the appropriateness of inter-hospital neurological transfers utilizing the telemedicine, our study aimed to assess the differences in outcomes of inter-hospital transfers utilizing the service in relation to the need for neurological interventions. Methods: The pragmatic, retrospective analysis included 181 consecutive patients, who were emergently transferred from telestroke-affiliated regional medical centers between October 3, 2021, and May 3, 2022. In this exploratory study investigating the outcomes of telestroke-referred patients, patients receiving interventions were compared to those that did not following transfer to our tertiary center. Neurological interventions included mechanical thrombectomy (MT) and/or tissue plasminogen activator (tPA), craniectomy, electroencephalography (EEG), or external ventricular drain (EVD). Transfer mortality rate, discharge functional status defined by modified Rankin scale (mRS), neurological status defined by National Institutes of Health Stroke Scale (NIHSS), 30-day unpreventable readmission rate, 90-day clinical major adverse cardiovascular events (MACE), and 90-day mRS, and NIHSS were studied. We used χ2 or Fisher exact tests to evaluate the association between the intervention and categorical or dichotomous variables. Continuous or ordinal measures were compared using Wilcoxon rank-sum tests. All tests of statistical significance were considered to be significant at P < 0.05. Results: Among the 181 transferred patients, 114 (63%) received neuro-intervention and 67 (37%) did not. The death rate during the index admission was not statistically significant between the intervention and non-intervention groups (P = 0.196). The discharge NIHSS and mRS were worse in the intervention compared to the non-intervention (P < 0.05 each, respectively). The 90-day mortality and cardiovascular event rates were similar between intervention and non-intervention groups (P > 0.05 each, respectively). The 30-day readmission rates were also similar between the two groups (14% intervention vs. 13.4% non-intervention, P = 0.910). The 90-day mRS were not significantly different between intervention and non-intervention groups (median 3 (IQR: 1 - 6) vs. 2 (IQR: 0 - 6), P = 0.109). However, 90-day NIHSS was worse in the intervention compared to non-intervention group (median 2 (IQR: 0 - 11) vs. 0 (IQR: 0 - 3), P = 0.004). Conclusions: Telestroke is a valuable resource that expedites emergent neurological care via referral to a stroke center. However, not all transferred patients benefit from the transfer process. Future multicenter studies are warranted to study the effects or appropriateness of telestroke networks, and to better understand the patient characteristics, resources allocation, and transferring institutions to improve telestroke care.

The temporal relationship of paraneoplastic aquaporin-4-IgG seropositive neuromyelitis optica spectrum disorder (NMOSD) and breast cancer: a systematic review and meta-analysis.

OBJECTIVE: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune astrocytopathy with evidence of neuroinflammation and demyelination that affects the central nervous system and is mediated by aquaporin-4 (AQP4) immunoglobulin (IgG). AQP4-IgG may also be present in paraneoplastic syndromes secondary to malignancy such as breast cancer. METHODS: A systematic review and meta-analysis of the literature were completed using PubMed, Scopus, and ScienceDirect databases (CRD42022352109). RESULTS: A total of 12 publications, which included 19 cases, met the inclusion criteria and were assessed in both the qualitative and quantitative synthesis. The mean age was 51.26 years (SD: 13.12, SEM: 3.01), and 100% of the cases were reported in women. Speech abnormalities and symptoms of myelopathy were the most observed neurological manifestations. MRI often revealed longitudinally extensive transverse myelitis (LETM) involving the cervical spine. Three of 19 (15.9%) cases were diagnosed with NMOSD and breast cancer within the same month. Five of 19 (26.1%) cases had a diagnosis of breast cancer preceding that of NMOSD. Eight of 19 (42.1%) cases were diagnosed with breast cancer after NMOSD. The median time of breast cancer diagnosis was 1.0 months (range 216 months) after NMOSD. CONCLUSIONS: The diagnosis of breast cancer most often occurs after the onset of the paraneoplastic NMOSD symptoms. However, a wide time range for the diagnosis of breast cancer was observed both before and after the onset of neurological symptoms. Older women with a new diagnosis of NMOSD should be considered for frequent breast cancer screening.

COVID-19 in the intensive care unit: Unmasking the critical factors impacting patient survival.

In the midst of the coronavirus disease 2019 (COVID-19) pandemic, intensive care units (ICUs) around the world have been pushed to their limits as they grapple with the effects of the severe acute respiratory syndrome coronavirus 2 virus. Identifying prognostic factors that influence mortality in COVID-19 patients admitted to the ICU could offer valuable insights for clinicians seeking to prevent disease progression. A retrospective analysis was conducted on COVID-19 patients admitted to the ICU between January and September 2020. The analysis considered patient demographics, comorbidities, neurological and non-neurological symptoms, as well as laboratory markers. The multivariate logistic regression analysis aims to uncover associations between these factors and patient outcomes. Of the 387 patients included in this study, nearly half (48.5%) of the ICU patients succumbed to COVID-19. Factors that contributed to increased mortality included being 60 years of age or older, impaired consciousness, lung disease, elevated international normalized ratio (INR), and elevated blood urea nitrogen (BUN) levels. Surprisingly, symptoms such as dizziness/lightheadedness, myalgia, and headache were associated with a higher likelihood of survival. In addition, elevated D-dimer and aspartate aminotransferase (AST) levels, as well as lymphopenia, were more commonly observed in deceased patients. The study concluded that those who died in the ICU tended to be older, white, and burdened with more comorbidities and impaired consciousness. With the intriguing link between specific symptoms and survival, further research is essential to uncover the underlying pathophysiological mechanisms that influence ICU patient outcomes in the context of COVID-19.

Targeting NMDA Receptor Complex in Management of Epilepsy.

N-methyl-D-aspartate receptors (NMDARs) are widely distributed in the central nervous system (CNS) and play critical roles in neuronal excitability in the CNS. Both clinical and preclinical studies have revealed that the abnormal expression or function of these receptors can underlie the pathophysiology of seizure disorders and epilepsy. Accordingly, NMDAR modulators have been shown to exert anticonvulsive effects in various preclinical models of seizures, as well as in patients with epilepsy. In this review, we provide an update on the pathologic role of NMDARs in epilepsy and an overview of the NMDAR antagonists that have been evaluated as anticonvulsive agents in clinical studies, as well as in preclinical seizure models.

Neurosyphilis presenting with focal middle cerebral artery stenosis and acute ischemic stroke: A case report.

Despite widespread screening and active management of syphilis infection, the rate of secondary and tertiary syphilis has increased over the past decade in the United States, especially with human immunodeficiency virus co-infection. We report a case of ischemic strokes in the middle cerebral artery (MCA) territory with focal stenosis of the left M1 segment of the MCA resulting from neurosyphilis with manifestation of subacute intermittent right-sided hemi-body numbness and transient word finding difficulties in a young adult with no prior known history of syphilis or significant cerebrovascular risk factors. A diagnostic cerebral angiogram was done which was initially concerning for possibility of reversible cerebral vasoconstriction syndrome (RCVS). The serum Treponema pallidum RPR testing resulted positive (1:32 titer) as well as subsequent reactive cerebrospinal fluid (CSF) VDRL test (ratio, 1:8). The patient was treated with intravenous ceftriaxone as well as verapamil and recovered without any residual deficits. To the best of our knowledge, this is the first reported evidence of possible RCVS in a case of neurosyphilis and related ischemic stroke. This case underscores the importance of evaluation for syphilis in young patients with fewer known vascular risk factors, who present with an ischemic stroke. Given the higher rates of stroke recurrence in neurosyphilis relative to few other stroke risk factors, early diagnosis, and treatment is furthermore essential to prevent disease progression.

Cortical Spreading Depolarizations and Clinically Measured Scalp EEG Activity After Aneurysmal Subarachnoid Hemorrhage and Traumatic Brain Injury.

BACKGROUND: Spreading depolarizations (SDs) are associated with worse outcome following subarachnoid hemorrhage (SAH) and traumatic brain injury (TBI), but gold standard detection requires electrocorticography with a subdural strip electrode. Electroencephalography (EEG) ictal-interictal continuum abnormalities are associated with poor outcomes after TBI and with both delayed cerebral ischemia (DCI) and poor outcomes after SAH. We examined rates of SD detection in patients with SAH and TBI with intraparenchymal and subdural strip electrodes and assessed which continuous EEG (cEEG) measures were associated with intracranially quantified SDs. METHODS: In this single-center cohort, we included patients with SAH and TBI undergoing ≥ 24 h of interpretable intracranial monitoring via eight-contact intraparenchymal or six-contact subdural strip platinum electrodes or both. SDs were rated according to established consensus criteria and compared with cEEG findings rated according to the American Clinical Neurophysiology Society critical care EEG monitoring consensus criteria: lateralized rhythmic delta activity, generalized rhythmic delta activity, lateralized periodic discharges, generalized periodic discharges, any ictal-interictal continuum, or a composite scalp EEG tool for seizure risk estimation: the 2HELPS2B score. Among patients with SAH, cEEG was assessed for validated DCI biomarkers: new or worsening epileptiform abnormalities and new background deterioration. RESULTS: Over 6 years, SDs were recorded in 5 (18%) of 28 patients recorded with intraparenchymal electrodes and 4 (40%) of 10 patients recorded with subdural strip electrodes. There was no significant association between occurrence of SDs and day 1 cEEG findings (American Clinical Neurophysiology Society main terms lateralized periodic discharges, generalized periodic discharges, lateralized rhythmic delta activity, or seizures, individually or in combination). After SAH, established cEEG DCI predictors were not associated with SDs. CONCLUSIONS: Intraparenchymal recordings yielded low rates of SD, and documented SDs were not associated with ictal-interictal continuum abnormalities or other cEEG DCI predictors. Identifying scalp EEG correlates of SD may require training computational EEG analytics and use of gold standard subdural strip electrocorticography recordings.