Microstructural Changes in Intraretinal Layers and Macular Structures of People with Epilepsy Measured Using Optical Coherence Tomography.

Introduction: Epilepsy is a network disorder that can cause alterations in retinal morphology due to microstructural changes in the brain. The aim of our study was to use spectral optical coherence tomography (OCT) to assess the possible effects of neuronal degeneration on the intraretinal layers and macular structures of people with epilepsy and epilepsy subgroups. Methods: We enrolled 52 consecutive people with epilepsy (37 females, 15 males; mean age 29.8±9.9 years; range, 17-48 years) and 40 healthy volunteers (27 females, 13 males; mean age 33.3±10.2 years; range, 19-49 years) in this study. Both eyes of all participants were assessed by using spectral-domain OCT. Optical coherence tomography was used to assess the thickness of the peripapillary retinal nerve fiber layer (RNFL), ganglion cell layer-inner plexiform layer (GCC-IPL), central macula, and central macular volume. Results: In comparison to healthy controls, people with epilepsy showed a thinner GCC-IPL in the superior and superior-nasal quadrants, as well as reduced macular thickness and macular volume (p<0.05). The thickness of the GCC-IPL layer in the superior and inferior subquadrants was negatively affected by frequent seizures (>5 seizures/year), polytherapy, and long-duration of epilepsy (≥10 years) (p<0.05). However, we did not find any other statistically significant associations between OCT measurements, age, sex, and epilepsy type (focal and generalized onset epilepsy). Conclusion: Individuals with epilepsy exhibited microstructural alterations in the retinal layers, primarily in the superior and inferior quadrants. Frequent seizures, polytherapy, and long-duration of epilepsy may result in neuronal damage in the afferent visual system.

Neurofilament light (NfL) concentrations in patients with epilepsy with recurrent isolated seizures: Insights from a clinical cohort study.

PURPOSE: To detect possible neuronal damage due to recurrent isolated seizures in patients with epilepsy in a clinical routine setting. METHODS: We measured the serum concentrations of neurofilament light chain (sNfL) in 46 outpatients with an at least monthly occurrence (self-reported) of generalized tonic-clonic seizures in the six months prior to the study and in 49 patients who had been seizure free (self-reported) for at least one year. We assigned the patients with seizure activity into groups with moderate and high seizure frequency. We measured sNfL with a highly sensitive single molecule array (Simoa). RESULTS: The majority (94 %) of all patients with epilepsy had sNfL values within the age adjusted reference ranges of our laboratory. Three patients with and three patients without seizure activity (each 3 %) showed elevated sNfL concentrations. Age adjusted sNfL concentrations did not differ significantly between patients with and without seizure activity in the total sample or in the female subgroup. In contrast, NfL concentrations were significantly higher in male patients with seizure activity and highest in the subgroup of those with high seizure activity, but were only above the reference range in two patients. sNfL concentrations did not differ between focal and generalized epilepsies and between genetic and structural etiologies. CONCLUSIONS: The sNfL concentrations in patients with epilepsy and healthy patients did not differ significantly. The finding of higher sNfL concentrations in males with self-reported seizure activity should be viewed with utmost caution because the difference was small and only two male patients showed sNfL concentrations above the reference range.

Clinical and paraclinical features of first unprovoked seizures in the elderly.

PURPOSE: The prevalence of unprovoked seizures and epilepsy rises significantly in later life stages. This study examines various factors in elderly patients (over 65 years) with their first unprovoked seizures, comparing findings with younger patients. METHODS: We analyzed electronic medical records of individuals with first unprovoked seizures retrospectively. Diagnosis was based on patient history and witness accounts, and exclusion of other potential causes. Data included demographics, physical examination, seizure characteristics, neuroimaging, EEG findings, laboratory markers, potential causes, prescribed anti-seizure medications (ASMs) at diagnosis and follow-up, seizure-related injuries and hospital stay length. RESULTS: We enrolled 391 patients (mean age 73.02 ± 16.5, 219 females). Most had late-onset (≥65 years) seizures (n = 295, 75.5 %). Status epilepticus was diagnosed in 10.2 %, more in the late-onset group. Elderly patients most often had focal seizures with impaired consciousness, while younger patients had focal to bilateral tonic-clonic seizures. (55.9 % vs 36.5 %). Late-onset seizures were linked to cerebrovascular diseases, small vessel disease, and cerebral atrophy, while early-onset cases were associated with brain tumors or unknown causes. Brain imaging revealed potentially epileptogenic abnormalities in 59.1 %. Positive paraneoplastic or autoimmune antibodies were found in 0.8 %. Abnormal EEGs were present in 25.9 %, more in the late-onset group. Most patients were discharged with levetiracetam (LEV) or lamotrigine (LTG) monotherapy. Nine patients with late-onset seizures died during in-hospital follow-up. CONCLUSION: Our findings can contribute to the improved identification and characterization of patients with late-onset seizures, facilitating targeted diagnostics and appropriate treatment in this challenging patient population.

Generalized Peripheric Nerve Hyperexcitability with Neuropathy: Case Series with Long-Term Outcome.

Introduction: Peripheric nerve hyperexcitability (PNH) syndromes are a rare, heterogenous group of diseases characterized by continuous muscle overactivity due to spontaneous discharges of the lower motor neurons. Case Series: Here we report four patients presented with painful cramps, generalized muscle twitches and lower extremity weakness. All patients had evidence of neuropathy and neuromyotonic discharges on electrodiagnostic studies. Screening for a broad panel of anti-neuronal antibodies proved uncharacterized neuropil antibodies in one patient. Despite extensive serologic and genetic investigations, no definitive etiology was found in our cohort. One out of three patients responded well to immunotherapy. No other diseases including malignancy appeared for 1.5-3 years follow-up duration. Conclusion: Our case series indicate a putatively high prevalence of neuropathy in PNH and emphasize anti-neuronal antibody positivity and early diagnosis as potential favorable prognostic factors.

Electrodiagnostic methods to verify Guillain-Barré syndrome subtypes in Istanbul: A prospective multicenter study.

BACKGROUND AND AIMS: This study aimed to identify the clinical characteristics and electrodiagnostic subtypes of Guillain-Barré syndrome (GBS) in Istanbul. METHODS: Patients with GBS were prospectively recruited between April 2019 and March 2022 and two electrodiagnostic examinations were performed on each patient. The criteria of Ho et al., Hadden et al., Rajabally et al., and Uncini et al. were compared for the differentiation of demyelinating and axonal subtypes, and their relations with anti-ganglioside antibodies were analyzed. RESULTS: One hundred seventy-seven patients were included, 69 before the coronavirus disease 2019 pandemic (April 2019-February 2020) and 108 during the pandemic (March 2020-March 2022), without substantial changes in monthly frequencies. As compared with the criteria of Uncini et al., demyelinating GBS subtype diagnosis was more frequent according to the Ho et al. and Hadden et al. criteria (95/162, 58.6% vs. 110/174, 63.2% and 121/174, 69.5%, respectively), and less frequent according to Rajabally et al.'s criteria (76/174, 43.7%). Fourteen patients' diagnoses made using Rajabally et al.'s criteria were shifted to the other subtype with the second electrodiagnostic examination. Of the 106 analyzed patients, 22 had immunoglobulin G anti-ganglioside antibodies (14 with the axonal subtype). They had less frequent sensory symptoms (54.5% vs. 83.1%, p = 0.009), a more frequent history of previous gastroenteritis (54.5% vs. 22.9%, p = 0.007), and a more severe disease as compared with those without antibodies. INTERPRETATION: Serial electrodiagnostic examinations are more helpful for accurate subtype diagnosis of GBS because of the dynamic pathophysiology of the disease. We observed no significant increase in GBS frequency during the pandemic in this metropolis.

Diagnostic value of "dysphagia limit" for neurogenic dysphagia: 17 years of experience in 1278 adults.

OBJECTIVE: Neurogenic dysphagia (ND) is a prevalent condition that accounts for significant mortality and morbidity worldwide. Screening and follow-up are critical for early diagnosis and management which can mitigate its complications and be cost-saving. The aims of this study are to provide a comprehensive investigation of the dysphagia limit (DL) in a large diverse cohort and to provide a longitudinal assessment of dysphagia in a subset of subjects. METHODS: We developed a quantitative and noninvasive method for objective assessment of dysphagia by using laryngeal sensor and submental electromyography. DL is the volume at which second or more swallows become necessary to swallow the whole amount of bolus. This study represents 17 years experience with the DL approach in assessing ND in a cohort of 1278 adult subjects consisting of 292 healthy controls, 784 patients with dysphagia, and 202 patients without dysphagia. A total of 192 of all patients were also reevaluated longitudinally over a period of 1-19 months. RESULTS: DL has 92% sensitivity, 91% specificity, 94% positive predictive value, and 88% negative predictive value with an accuracy of 0.92. Patients with ALS, stroke, and movement disorders have the highest sensitivity (85-97%) and positive predictive value (90-99%). The clinical severity of dysphagia has significant negative correlation with DL (r=-0.67, p<0.0001). CONCLUSIONS: We propose the DL as a reliable, quick, noninvasive, quantitative test to detect and follow both clinical and subclinical dysphagia and it can be performed in an EMG laboratory. SIGNIFICANCE: Our study provides specific quantitative features of DL test that can be readily utilized by the neurologic community and nominates DL as an objective and robust method to evaluate dysphagia in a wide range of neurologic conditions.

DNAJC6 is responsible for juvenile parkinsonism with phenotypic variability.

Familial parkinson's disease is both clinically and genetically heterogeneous. By mapping the disease locus with a lod score of 5.13 to a < 3.5 Mbp region at 1p31.3 in a consanguineous family and subsequent exome sequencing analysis, we identified homozygous truncating mutation p.Q734X in DNAJC6. Four members of the family were afflicted with juvenile parkinsonism that presented with mental retardation, pyramidal signs and epilepsy, as well as varying degrees of a progressive neurological disease. Recently a splicing mutation in the same gene was reported in two brothers with juvenile parkinsonism that was not L-Dopa responsive and not accompanied by pyramidal signs or mental retardation. Also, an 80-kb deletion that included DNAJC6 sequences was identified in a boy reported as having obesity, epilepsy and mental retardation but not any signs of parkinsonism. The phenotype of our study family resembles both of those families, which among themselves do not share any clinical features. Our findings further establish DNAJC6 as a juvenile parkinsonism gene, and expand the spectrums of the parkinsonism phenotype and DNAJC6 mutation. DNAJC6 encodes the neuronal co-chaperone auxilin. We found that its transcript is highly significantly more abundant in brain as compared to the non-neural tissues assayed.

Post-ischemic Holmes' tremor of the lower extremities.

Holmes' tremor, which is known to occur as a result of different lesions centered in the brain stem, cerebellum and thalamus, is a tremor of low frequency, mostly below 4.5 Hz (Deuschl and Bergman in Mov Disord 17(suppl 3):S41­S48, 2002). We present a patient who developed a tremor, mostly involving her lower extremities, secondary to an ischemic infarct affecting the cerebellum, thalamus and midbrain. Attempts at medical treatment with levodopa, quetiapine and levetirecetam all failed. However, pribedil, a dopaminergic receptor-stimulating agent, successfully improved the tremor. Our case is interesting as published reports generally focus on tremors limited to the upper extremities except for one reported case of Holmes' tremor involving the lower extremities more severely (Walker et al. in Mov Disord 22(2):272­274, 2007). It also demonstrates that dopaminergic receptor stimulating agents should be tested before considering invasive therapies.