Neurological Health: Not Merely the Absence of Disease: Current Wellbeing Instruments Across the Spectrum of Neurology.

OBJECTIVE: Well-being and quality of life can vary independently of disease. Instruments measuring well-being and quality of life are commonly used in neurology, but there has been little investigation into the extent in which they accurately measure wellbeing/quality of life or if they merely reflect a diseased state of an individual. DESIGN: Systematic searches, thematic analysis and narrative synthesis were undertaken. Individual items from instruments represented in ≥ 5 publications were categorised independently, without prior training, by five neurologists and one well-being researcher, as relating to 'disease-effect' or 'Well-being' with a study-created instrument. Items were additionally categorised into well-being domains. DATA SOURCES: MEDLINE, EMBASE, EMCARE and PsycINFO from 1990 to 2020 were performed, across the 13 most prevalent neurological diseases. RESULTS: 301 unique instruments were identified. Multiple sclerosis had most unique instruments at 92. SF-36 was used most, in 66 studies. 22 instruments appeared in ≥ 5 publications: 19/22 'well-being' outcome instruments predominantly measured disease effect (Fleiss kappa = .60). Only 1/22 instruments was categorised unanimously as relating to well-being. Instruments predominantly measured mental, physical and activity domains, over social or spiritual. CONCLUSIONS: Most neurological well-being or quality-of-life instruments predominantly measure disease effect, rather than disease-independent well-being. Instruments differed widely in well-being domains examined.

Time-frequency mapping of the rhythmic limb movements distinguishes convulsive epileptic from psychogenic nonepileptic seizures.

PURPOSE: A definite diagnosis of psychogenic nonepileptic seizures (PNES) usually requires in-patient video-electroencephalography (EEG) monitoring. Previous research has shown that convulsive psychogenic nonepileptic seizures (PNES) demonstrate a characteristic pattern of rhythmic movement artifact on the EEG. Herein we sought to examine the potential for time-frequency mapping of data from a movement-recording device (accelerometer) worn on the wrist as a diagnostic tool to differentiate between convulsive epileptic seizures and PNES. METHODS: Time-frequency mapping was performed on accelerometer traces obtained during 56 convulsive seizure-like events from 35 patients recorded during in-patient video-EEG monitoring. Twenty-six patients had PNES, eight had epileptic seizures, and one had both seizure types. The time-frequency maps were derived from fast Fourier transformations to determine the dominant frequency for sequential 2.56-s blocks for the course of each event. KEY FINDINGS: The coefficient of variation (CoV) of limb movement frequency for the PNES events was less than for the epileptic seizure events (median, 17.18% vs. 52.23%; p < 0.001). A blinded review of the time-frequency maps by an epileptologist was accurate in differentiating between the event types, that is, 38 (92.7%) of 41 and 6 (75%) of 8 nonepileptic and epileptic seizures, respectively, were diagnosed correctly, with seven events classified as "nondiagnostic." Using a CoV cutoff score of 32% resulted in similar classification accuracy, with 42 (93%) of 45 PNES and 10 (91%) of 11 epileptic seizure events correctly diagnosed. SIGNIFICANCE: Time-frequency analysis of data from a wristband movement monitor could be utilized as a diagnostic tool to differentiate between epileptic and nonepileptic convulsive seizure-like events.

The extent of resection of FDG-PET hypometabolism relates to outcome of temporal lobectomy.

A significant minority of patients undergoing surgery for medically refractory non-lesional temporal lobe epilepsy (TLE) continue to have seizures, but the reasons for this are uncertain. Fluorodeoxyglucose (FDG) PET shows hypometabolism in a majority of patients with non-lesional TLE, even in the absence of hippocampal atrophy. We examined whether the extent of resection of the area of FDG-PET hypometabolism influenced outcome following surgery for non-lesional TLE. Twenty-six patients who underwent temporal lobectomy for medically refractory TLE with at least 12 months follow-up were studied. The preoperative FDG-PET was compared with 20 non-epileptic controls using SPM99 to identify regions of significant hypometabolism (P < 0.0005, cluster > 200). This image was then co-registered to the postoperative MRI scan. The volume of the FDG-PET hypometabolism that lay within the area of the resected temporal lobe was calculated. The volume of temporal lobe resected was also calculated. Patients with a good outcome had a greater proportion of the total FDG-PET hypometabolism volume resected than those with a poor outcome (24.1% versus 11.8%, P = 0.02). There was no significant difference between the groups in the volume of temporal lobe resected (P = 0.86). Multivariate regression demonstrated that the extent of resection of the hypometabolism significantly correlated with outcome (P = 0.03), independent of the presence of hippocampal sclerosis (P = 0.03) and total brain volume of hypometabolism (P = 0.45). The extent of resection of the region of hypometabolism on the preoperative FDG-PET is predictive of outcome following surgery for non-lesional TLE. Strategies that tailor resection extent to regional hypometabolism may warrant further evaluation.

Depression in temporal lobe epilepsy surgery patients: an FDG-PET study.

PURPOSE: Depression is common in temporal lobe epilepsy (TLE) and after temporal lobectomy, and its etiology is obscure. In nonepileptic depression (including depression associated with other neurologic disorders), a consistent PET imaging finding is frontal lobe hypometabolism. Many TLE patients have hypometabolism involving frontal regions. Thus in data available from routine clinical assessments in an epilepsy surgery unit, we tested the hypothesis that the pattern of hypometabolism, particularly in the frontal lobe, may be associated with the depression seen in patients with TLE and TLE surgery. METHODS: We studied 23 medically refractory TLE patients who underwent anterior temporal lobectomy and who had preoperative FDG-PET scanning. All patients had pre- and postoperative psychiatric assessment. By using statistical parametric mapping (SPM-99), patterns of hypometabolism were compared between patients who had a preoperative history of depression (n=9) versus those who did not (n=14) and between those in whom postoperative depression developed (n=13) versus those in whom it did not (n=10). A significant region of hypometabolism was set at p<0.001 for a cluster of >or=20 contiguous voxels. RESULTS: Patients with a history of depression at any time preoperatively showed focal hypometabolism in ipsilateral orbitofrontal cortex compared with those who did not (t=4.64; p<0.001). Patients in whom depression developed postoperatively also showed hypometabolism in the ipsilateral orbitofrontal region (t=5.10; p<0.001). CONCLUSIONS: Although this study is methodologically limited, and other explanations merit consideration, orbitofrontal cortex dysfunction, already implicated in the pathophysiology of nonepileptic depression, may also be relevant to the depression of TLE and temporal lobectomy.

Dentatorubral-pallidoluysian atrophy in three generations, with clinical courses from nearly asymptomatic elderly to severe juvenile, in an Australian family of Macedonian descent.

We report a three-generation Caucasian family of Macedonian origin with dentatorubral-pallidoluysian atrophy (DRPLA), manifesting as very mild elderly onset, severe young adult onset, and severe childhood onset presentations in the three generations. The grandparental trinucleotide expansion size (52 repeats) is the smallest overtly pathogenic mutation yet reported. This 67-year-old man displayed only subtle neurological and cognitive deficits on formal examination and very slight signs on MRI. His son had developed a choreiform disorder at age 32 years, and by his 40s suffered severe dementia and motor decline. The grandson, the proband, presented as a teenager with progressive myoclonic epilepsy, dysarthria, ataxia, and cognitive decline, having manifesting learning difficulties from the age 5 years. Atrophin-1 expansion sizes of 52, 57, and 66 repeats were demonstrated in the three patients, respectively. Given an absence of any other indicative history in the family, we speculate that the mutation may have expanded from a 'high-end' normal allele to a pathogenic size at the grandfather's conception, or that one of his parents may have had a pathogenic mutation at the lowest end of the expanded range.

Tiagabine-induced generalised non convulsive status epilepticus in patients with lesional focal epilepsy.

PURPOSE: To report 3 cases with focal lesional epilepsy that had non-convulsive status epilepticus (NCSE) induced by treatment with tiagabine (TGB) and review the previously published cases. Drugs that enhance GABAnergic transmission are recognised to promote absence seizures in patients with generalised epilepsy syndromes and may on occasions even induce NCSE. However, that TGB can also induce NCSE in focal lesional epilepsy is not widely recognised in clinical practice. METHOD: The clinical history, EEG and MRI findings were reviewed in 3 patients with lesional focal epilepsy who presented to our epilepsy programs over a 12 month period with TGB-induced NCSE. All previously reported cases in the English medical literature were reviewed. RESULTS: The three patients had longstanding complex partial and secondarily generalised seizures refractory to multiple different anti-epileptic drugs. In two cases, MRI demonstrated a focal malformation of cortical development in the left parieto-occipital region and in the third left mesial temporal sclerosis. Following commencement of TGB in one patient and dose escalation in two, prolonged episodes of confusion and poor responsiveness were noted. Prolonged EEG monitoring demonstrated continuous high amplitude, generalised, 2-4 Hz delta activity with intermingled spikes during the episodes of unresponsiveness, consistent with NCSE. The clinical and EEG activity normalised following the administration of IV clonazepam followed by dose reduction or withdrawal of the TGB. Eleven previously reported cases of patients with partial epilepsy and a focal underlying lesion on MRI were identified, all of whom had similar features to that seen in our cases. CONCLUSIONS: These cases illustrate that TGB may induce generalised NCSE in patients with focal lesional epilepsy, in addition to those with generalised syndromes. We hypothesise that patients may have developed an acquired alteration in the sensitivity of their thalamocortical circuitry that renders them more sensitive to the effects of drugs that enhance GABAnergic activity.

"Convulsive" nonepileptic seizures have a characteristic pattern of rhythmic artifact distinguishing them from convulsive epileptic seizures.

PURPOSE: Approximately 30% of patients admitted for video-EEG monitoring have psychogenic nonepileptic seizures (PNES). Differentiation of "convulsive" PNES from convulsive seizures can be difficult. The EEG often displays rhythmic movement artifact that may resemble seizure activity and confound the interpretation. We sought to determine whether time-frequency mapping of the rhythmic EEG artifact during "convulsive" PNES reveals a pattern that differs from that of epileptic seizures. METHODS: EEGs from 15 consecutive patients with "convulsive" PNESs were studied with time-frequency mapping by using NEUROSCAN and compared with 15 patients with convulsive epileptic seizures. Fast Fourier transforms (FFTs) were performed to determine the dominant frequency for 1- to 2-s windows every 2 s through the seizures. RESULTS: The dominant frequency remained stable within a narrow range for the duration of the PNES, whereas in the epileptic seizures, it evolved through a wide range. The coefficient of variation of the frequency during the seizures was considerably less for patients without epilepsy (median, 15.0%; range, 7.2-23.7% vs. median, 58.0%; range, 34.8-92.1%; p < 0.001). The median frequency did not differ significantly between groups (4.2 vs. 4.6 Hz; p = 0.290). CONCLUSIONS: "Convulsive" PNES display a characteristic pattern on time-frequency mapping of the EEG artifact, with a stable, nonevolving frequency that is different from the evolving pattern seen during an epileptic seizure.