In patients with medically refractory epilepsy, resective surgery is the mainstay of therapy to achieve seizure freedom. However, ∼20-50% of cases have intractable seizures post-surgery due to the ...imprecise determination of epileptogenic zone. Recent intracranial studies suggest that high frequency oscillations between 80 and 200 Hz could serve as one of the consistent epileptogenicity biomarkers for localization of the epileptogenic zone. However, these high frequency oscillations are not adopted in the clinical setting because of difficult non-invasive detection. Here, we investigated non-invasive detection and localization of high frequency oscillations and its clinical utility in accurate pre-surgical assessment and post-surgical outcome prediction. We prospectively recruited 52 patients with medically refractory epilepsy who underwent standard pre-surgical workup including magnetoencephalography (MEG) followed by resective surgery after determination of the epileptogenic zone. The post-surgical outcome was assessed after 22.14 ± 10.05 months. Interictal epileptic spikes were expertly identified, and interictal epileptic oscillations across the neural activity frequency spectrum from 8 to 200 Hz were localized using adaptive spatial filtering methods. Localization results were compared with epileptogenic zone and resected cortex for congruence assessment and validated against the clinical outcome. The concordance rate of high frequency oscillations sources (80-200 Hz) with the presumed epileptogenic zone and the resected cortex were 75.0% and 78.8%, respectively, which is superior to that of other frequency bands and standard dipole fitting methods. High frequency oscillation sources corresponding with the resected cortex, had the best sensitivity of 78.0%, positive predictive value of 100% and an accuracy of 78.84% to predict the patient's surgical outcome, among all other frequency bands. If high frequency oscillation sources were spatially congruent with resected cortex, patients had an odds ratio of 5.67 and 82.4% probability of achieving a favourable surgical outcome. If high frequency oscillations sources were discordant with the epileptogenic zone or resection area, patient has an odds ratio of 0.18 and only 14.3% probability of achieving good outcome, and mostly tended to have an unfavourable outcome (χ2 = 5.22; P = 0.02; φ = -0.317). In receiver operating characteristic curve analyses, only sources of high-frequency oscillations demonstrated the best sensitivity and specificity profile in determining the patient's surgical outcome with area under the curve of 0.76, whereas other frequency bands indicate a poor predictive performance. Our study is the first non-invasive study to detect high frequency oscillations, address the efficacy of high frequency oscillations over the different neural oscillatory frequencies, localize them and clinically validate them with the post-surgical outcome in patients with medically refractory epilepsy. The evidence presented in the current study supports the fact that HFOs might significantly improve the presurgical assessment, and post-surgical outcome prediction, where it could widely be used in a clinical setting as a non-invasive biomarker.
Highlights • EEG of 9 patients with absence epilepsy were evaluated for occurrence of HFO. • HFOs were associated with inter-ictal generalized (241/454). • HFOs were associated with ictal generalized ...(634/884). • HFOs were associated with sporadic spike-wave discharges (51/100). • ICA with spectral analysis showed the mean frequency of HFOs was 96.4 ± 10.4 Hz.
BACKGROUND: Psychotherapy for people with acquired brain injury (ABI) is considered to be an important component of a holistic neuropsychological rehabilitation approach. This helps in making sense ...of the loss of the sense of self they experience. Gender, premorbid personality, and socio-cultural discourses guide this process of understanding. Narrative formulation takes these considerations into account and, thus, can be used for formulating therapeutic plans. AIM: To present a case report which highlights the use of narrative case formulation to understand the psychological, social, and cultural factors forming the dominant discourse of a woman with ABI. METHODS: Ms. VA, a 43-year-old female, presented herself with a diagnosis of hypoxic ischemic encephalopathy with small chronic infarcts with gliosis in the bilateral cerebellar hemisphere, myoclonic seizures, mild cognitive impairment, depression, generalized dystonia, and bronchial asthma. Along with neuropsychological rehabilitation and cognitive retraining, 25 sessions of psychotherapy using narrative formulation were performed. RESULTS: Following the therapy, microgains such as a developing strong therapeutic relationship, accommodating vulnerability in her narrative, and finding moments of independence and assertion within the constraints of ABI were observed. Acceptance of her current predicament vis-à-vis her lost self and finding meaning in her new self were facilitated. CONCLUSION: There is paucity of research detailing psychotherapeutic management of ABI, especially in India. Psychotherapy, particularly using narrative formulation, can be helpful in understanding the intersections of gender role and expectations, premorbid personality and ABI, and aiding the post-ABI rehabilitation and adjustment. Future work in this area can explore the socio-cultural aspects that play an important role in the therapy process.
Complex febrile seizures (CFS), a subset of paediatric febrile seizures (FS), have been studied for their prognosis, epileptogenic potential and neurocognitive outcome. We evaluated their functional ...connectivity differences with simple febrile seizures (SFS) in children with recent-onset FS. Resting-state fMRI (rs-fMRI) datasets of 24 children with recently diagnosed FS (SFS-n = 11; CFS-n = 13) were analysed. Functional connectivity (FC) was estimated using time series correlation of seed region-to-whole-brain-voxels and network topology was assessed using graph theory measures. Regional connectivity differences were correlated with clinical characteristics (FDR corrected p < 0.05). CFS patients demonstrated increased FC of the bilateral middle temporal pole (MTP), and bilateral thalami when compared to SFS. Network topology study revealed increased clustering coefficient and decreased participation coefficient in basal ganglia and thalamus suggesting an inefficient-unbalanced network topology in patients with CFS. The number of seizure recurrences negatively correlated with the integration of Left Thalamus (r = - 0.58) and FC of Left MTP to 'Right Supplementary Motor and left Precentral' gyrus (r = - 0.53). The FC of Right MTP to Left Amygdala, Putamen, Parahippocampal, and Orbital Frontal Cortex (r = 0.61) and FC of Left Thalamus to left Putamen, Pallidum, Caudate, Thalamus Hippocampus and Insula (r 0.55) showed a positive correlation to the duration of the longest seizure. The findings of the current study report altered connectivity in children with CFS proportional to the seizure recurrence and duration. Regardless of the causal/consequential nature, such observations demonstrate the imprint of these disease-defining variables of febrile seizures on the developing brain.
The significance of fiducial marker detection in neuroimaging cannot be overstated, as these markers serve as vital reference points for accurate spatial alignment during image registration. Our ...proposed model addresses challenges in consistent marker placement and variability during MRI scanning, ensuring reliable localization for subsequent analysis. This paper introduces an innovative approach to fiducial marker detection in T1-weighted MRI volumes, specifically targeting the Left Preauricular Point (LPA), Right Pre-auricular Point (RPA), and Nasion. The implementation employs a 3D Convolutional Neural Network (CNN) to achieve precise localization of these crucial anatomical landmarks. Operating on a high-performance system our algorithm demonstrated exceptional accuracy and sensitivity using MATLAB R2023a as the primary tool for development and evaluation. Rigorous experiments on a diverse dataset showcased the algorithm's robust performance. For RPA detection, the model achieved 96.55% accuracy, emphasizing sensitivity (96.78% recall) and precision (96.35%). LPA detection demonstrated an impressive accuracy of 96.88%, with heightened sensitivity (96.95%) and precision (96.83%). The nasion detection process exhibited precise localization, with a Mean Square Error (MSE) of 0.3439 for 36 volume data. These results highlight the algorithm's potential to enhance accuracy and efficiency in fiducial point detection for improved neuroimaging studies.
Reports of spectrum of clinical manifestations in
PMP22
gene–associated neuropathies (duplication/mutations) are scarce. To identify the frequency of
PMP22
gene variations and establish their ...genotype-phenotype correlation. Patients with suspected genetic demyelinating neuropathy (
n
= 128) underwent evaluation for copy number variations and point mutations in
PMP22
gene by multiplex ligation-dependent probe amplification (MLPA) and direct sequencing respectively. Of these, only 27 patients (M:F:19:8) from 18 families had
PMP22
gene–associated neuropathy; they were subsequently analyzed for genotype-phenotype correlation. Twenty-five patients had
PMP22
duplication while two patients had
PMP22
missense mutations (p.A114V and p.L80P). Age at onset of neuropathy ranged from infancy to 63 years and symptom duration ranged from 2 to 32 years. Cranial nerve dysfunction in the form of ptosis, ophthalmoplegia, bifacial weakness, and sensorineural hearing loss was observed in addition to a number of systemic features. Three patients were asymptomatic. All except one patient were ambulant. Velocity of median nerve and amplitude of evoked motor responses from common peroneal nerve were significantly reduced in male patients. There was significantly worse disability in the late-onset group as compared with the early-onset group. Otherwise, the mean age at onset, frequency of skeletal deformities, patterns of motor weakness, muscle stretch reflexes, sensory impairment, disability rating scales, and electrophysiological parameters were comparable irrespective of gender, onset age, family history and ulnar nerve conduction velocities. The relatively low frequency of
PMP22
duplication in the present cohort warrants a more comprehensive search to establish the genetic etiology. Further research into the role of other genetic variants as well as modifier genes and their effect on phenotypic heterogeneity is indicated.
Background
Mitochondrial disorders are clinically complex and have highly variable phenotypes among all inherited disorders. Mutations in mitochon drial DNA (mtDNA) and nuclear genome or both have ...been reported in mitochondrial diseases suggesting common pathophysiological pathways. Considering the clinical heterogeneity of mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) phenotype including focal neurological deficits, it is important to look beyond mitochondrial gene mutation.
Methods
The clinical, histopathological, biochemical analysis for OXPHOS enzyme activity, and electron microscopic, and neuroimaging analysis was performed to diagnose 11 patients with MELAS syndrome with a multisystem presentation. In addition, whole exome sequencing (WES) and whole mitochondrial genome sequencing were performed to identify nuclear and mitochondrial mutations.
Results
Analysis of whole mtDNA sequence identified classical pathogenic mutation m.3243A > G in seven out of 11 patients. Exome sequencing identified pathogenic mutation in several nuclear genes associated with mitochondrial encephalopathy, sensorineural hearing loss, diabetes, epilepsy, seizure and cardiomyopathy (
POLG
,
DGUOK
,
SUCLG2
,
TRNT1
,
LOXHD1
,
KCNQ1
,
KCNQ2
,
NEUROD1
,
MYH7
) that may contribute to classical mitochondrial disease phenotype alone or in combination with m.3243A > G mutation.
Conclusion
Individuals with MELAS exhibit clinical phenotypes with varying degree of severity affecting multiple systems including auditory, visual, cardiovascular, endocrine, and nervous system. This is the first report to show that nuclear genetic factors influence the clinical outcomes/manifestations of MELAS subjects alone or in combination with m.3243A > G mutation.
Epilepsy: Indian perspective Santhosh, Nandanavana Subbareddy; Sinha, Sanjib; Satishchandra, Parthasarathy
Annals of the Indian Academy of Neurology,
03/2014, Letnik:
17, Številka:
Suppl 1
Journal Article
Recenzirano
Odprti dostop
There are 50 million people living with epilepsy worldwide, and most of them reside in developing countries. About 10 million persons with epilepsy are there in India. Many people with active ...epilepsy do not receive appropriate treatment for their condition, leading to large treatment gap. The lack of knowledge of antiepileptic drugs, poverty, cultural beliefs, stigma, poor health infrastructure, and shortage of trained professionals contribute for the treatment gap. Infectious diseases play an important role in seizures and long-term burden causing both new-onset epilepsy and status epilepticus. Proper education and appropriate health care services can make tremendous change in a country like India. There have been many original researches in various aspects of epilepsy across India. Some of the geographically specific epilepsies occur only in certain regions of our country which have been highlighted by authors. Even the pre-surgical evaluation and epilepsy surgery in patients with drug-resistant epilepsy is available in many centers in our country. This article attempts to provide a complete preview of epilepsy in India.
Wilson disease (WD) is an autosomal recessive disorder, characterized by excessive deposition of copper in various parts of the body, mainly in the liver and brain. It is caused by mutations in ...ATP7B. We report here the genetic analysis of 102 WD families from a south Indian population. Thirty-six different ATP7B mutations, including 13 novel ones p.Ala58fs*19, p.Lys74fs*9, p.Gln281*, p.Pro350fs*12, p.Ser481*, p.Leu735Arg, p.Val752Gly, p.Asn812fs*2, p.Val845Ala, p.His889Pro, p.Ile1184fs*1, p.Val1307Glu and p.Ala1339Pro, were identified in 76/102 families. Interestingly, the mutation analysis of affected individuals in two families identified two different homozygous mutations in each family, and thus each affected individual from these families harbored two mutations in each ATP7B allele. Of 36 mutations, 28 were missense, thus making them the most prevalent mutations identified in the present study. Nonsense, insertion and deletion represented 3/36, 2/36 and 3/36 mutations, respectively. The haplotype analysis suggested founder effects for all the 14 recurrent mutations. Our study thus expands the mutational landscape of ATP7B with a total number of 758 mutations. The mutations identified during the present study will facilitate carrier and pre-symptomatic detection, and prenatal genetic diagnosis in affected families.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Polymerase γ catalytic subunit (
POLG
), a nuclear gene, encodes the enzyme responsible for mitochondrial DNA (mtDNA) replication.
POLG
mutations are a major cause of inherited mitochondrial ...diseases. They present with varied phenotypes, age of onset, and severity. Reports on
POLG
mutations from India are limited. Hence, this study aimed to describe the clinico-pathological and molecular observations of
POLG
mutations. A total of 446 patients with clinical diagnosis of mitochondrial disorders were sequenced for all exons and intron-exon boundaries of
POLG
. Of these, 19 (4.26%) patients (M:F: 10:9) had
POLG
mutations. The age of onset ranged from 5 to 55 years with an overlapping phenotypic spectrum. Ptosis, peripheral neuropathy, seizures, and ataxia were the common neurological features observed. The most common clinical phenotype was chronic progressive external ophthalmoplegia (CPEO) and CPEO plus (
n
= 14). Muscle biopsy showed characteristic features of mitochondrial myopathy in fourteen patients (14/19) and respiratory chain enzyme deficiency in eleven patients (11/19). Multiple mtDNA deletions were seen in 47.36% (9/19) patients. Eight pathogenic
POLG
variations including two novel variations (p.G132R and p.V1106A) were identified. The common pathogenic mutation identified was p.L304R, being present in eight patients (42.1%) predominantly in the younger age group followed by p.W748S in four patients (21%). To the best of our knowledge, this is the first extensive study from India, highlights the clinico-pathological and molecular spectrum of
POLG
mutations.
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