Treating Rhythmic and Periodic EEG Patterns in Comatose Survivors of Cardiac Arrest.

BACKGROUND: Whether the treatment of rhythmic and periodic electroencephalographic (EEG) patterns in comatose survivors of cardiac arrest improves outcomes is uncertain. METHODS: We conducted an open-label trial of suppressing rhythmic and periodic EEG patterns detected on continuous EEG monitoring in comatose survivors of cardiac arrest. Patients were randomly assigned in a 1:1 ratio to a stepwise strategy of antiseizure medications to suppress this activity for at least 48 consecutive hours plus standard care (antiseizure-treatment group) or to standard care alone (control group); standard care included targeted temperature management in both groups. The primary outcome was neurologic outcome according to the score on the Cerebral Performance Category (CPC) scale at 3 months, dichotomized as a good outcome (CPC score indicating no, mild, or moderate disability) or a poor outcome (CPC score indicating severe disability, coma, or death). Secondary outcomes were mortality, length of stay in the intensive care unit (ICU), and duration of mechanical ventilation. RESULTS: We enrolled 172 patients, with 88 assigned to the antiseizure-treatment group and 84 to the control group. Rhythmic or periodic EEG activity was detected a median of 35 hours after cardiac arrest; 98 of 157 patients (62%) with available data had myoclonus. Complete suppression of rhythmic and periodic EEG activity for 48 consecutive hours occurred in 49 of 88 patients (56%) in the antiseizure-treatment group and in 2 of 83 patients (2%) in the control group. At 3 months, 79 of 88 patients (90%) in the antiseizure-treatment group and 77 of 84 patients (92%) in the control group had a poor outcome (difference, 2 percentage points; 95% confidence interval, -7 to 11; P = 0.68). Mortality at 3 months was 80% in the antiseizure-treatment group and 82% in the control group. The mean length of stay in the ICU and mean duration of mechanical ventilation were slightly longer in the antiseizure-treatment group than in the control group. CONCLUSIONS: In comatose survivors of cardiac arrest, the incidence of a poor neurologic outcome at 3 months did not differ significantly between a strategy of suppressing rhythmic and periodic EEG activity with the use of antiseizure medication for at least 48 hours plus standard care and standard care alone. (Funded by the Dutch Epilepsy Foundation; TELSTAR ClinicalTrials.gov number, NCT02056236.).

The natural history of progressive myoclonus ataxia.

Progressive myoclonus ataxia (PMA) is a rare clinical syndrome characterized by the presence of progressive myoclonus and ataxia, and can be accompanied by mild cognitive impairment and infrequent epileptic seizures. This is the first study to describe the natural history of PMA and identify clinical, electrophysiological, and genetic features explaining the variability in disease progression. A Dutch cohort of consecutive patients meeting the criteria of the refined definition of PMA was included. The current phenotype was assessed during in-person consultation by movement disorders experts, and retrospective data was collected to describe disease presentation and progression, including brain imaging and therapy efficacy. Extensive genetic and electrophysiological tests were performed. The presence of cortical hyperexcitability was determined, by either the identification of a cortical correlate of myoclonic jerks with simultaneous electromyography-electroencephalography or a giant somatosensory evoked potential. We included 34 patients with PMA with a median disease duration of 15 years and a clear progressive course in most patients (76%). A molecular etiology was identified in 82% patients: ATM, CAMTA1, DHDDS, EBF3, GOSR2, ITPR1, KCNC3, NUS1, POLR1A, PRKCG, SEMA6B, SPTBN2, TPP1, ZMYND11, and a 12p13.32 deletion. The natural history is a rather homogenous onset of ataxia in the first two years of life followed by myoclonus in the first 5 years of life. Main accompanying neurological dysfunctions included cognitive impairment (62%), epilepsy (38%), autism spectrum disorder (27%), and behavioral problems (18%). Disease progression showed large variability ranging from an epilepsy free PMA phenotype (62%) to evolution towards a progressive myoclonus epilepsy (PME) phenotype (18%): the existence of a PMA-PME spectrum. Cortical hyperexcitability could be tested in 17 patients, and was present in 11 patients and supported cortical myoclonus. Interestingly, post-hoc analysis showed that an absence of cortical hyperexcitability, suggesting non-cortical myoclonus, was associated with the PMA-end of the spectrum with no epilepsy and milder myoclonus, independent of disease duration. An association between the underlying genetic defects and progression on the PMA-PME spectrum was observed. By describing the natural history of the largest cohort of published patients with PMA so far, we see a homogeneous onset with variable disease progression, in which phenotypic evolution to PME occurs in the minority. Genetic and electrophysiological features may be of prognostic value, especially the determination of cortical hyperexcitability. Furthermore, the identification of cortical and non-cortical myoclonus in PMA helps us gain insight in the underlying pathophysiology of myoclonus.

Negative Myoclonus: Neurophysiological Study and Clinical Impact in Progressive Myoclonus Ataxia.

INTRODUCTION: Negative myoclonus (NM) is an involuntary movement caused by a sudden interruption of muscular activity, resulting in gait problems and falls. OBJECTIVE: To establish frequency, clinical impact, and neurophysiology of NM in progressive myoclonus ataxia (PMA) patients. METHODS: Clinical, neurophysiological, and genetic data of 14 PMA individuals from University Medical Centre Groningen (UMCG) Expertise Center Movement Disorder Groningen were retrospectively collected. Neurophysiological examination included video-electromyography-accelerometry assessment in all patients and electroencephalography (EEG) examination in 13 individuals. Jerk-locked (or silent period-locked) back-averaging and cortico-muscular coherence (CMC) analysis aided the classification of myoclonus. RESULTS: NM was present in 6 (NM+) and absent in 8 (NM-) PMA patients. NM+ individuals have more frequent falls (100% vs. 37.5%) and higher scores on the Gross Motor Function Classification System (GMFCS) (4.3 ±0.74 vs. 2.5 ±1.2) than NM- individuals. Genetic background of NM+ included GOSR2 and SEMA6B, while that of NM- included ATM, KCNC3, NUS1, STPBN2, and GOSR2. NM was frequently preceded by positive myoclonus (PM) and silent-period length was between 88 and 194 ms. EEG epileptiform discharges were associated with NM in 2 cases. PM was classified as cortical in 5 NM+ and 2 NM- through EEG inspection, jerk-locked back-averaging, or CMC analysis. DISCUSSION: Neurophysiological examination is crucial for detecting NM that could be missed on clinical examination due to a preceding PM. Evidence points to a cortical origin of NM, an association with more severe motor phenotype, and suggests the presence of genetic disorders causing either a PMA or progressive myoclonus epilepsy, rather than pure PMA phenotype. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Substantiating the Short Burst Duration in Cortical Myoclonus.

BACKGROUND: Myoclonus is characterized by involuntary, shock-like movements, of which cortical (CM) and non-cortical myoclonus (NCM) are most common. Electrophysiology can help differentiate between these subtypes; however, the diagnostic value of several features is largely unknown. OBJECTIVE: This study aims to determine the diagnostic value of the burst duration in distinguishing CM and NCM. METHODS: We manually identified the burst duration of 8 patients with CM, confirmed by electromyography-electroencephalography registration or somatosensory-evoked potentials, and 19 patients with NCM, suspected due to a myoclonus-dystonia phenotype (MYC/DYT-SGCE positive and negative). RESULTS: The sensitivity and specificity were calculated to assess the diagnostic value. The burst duration of CM (31.1 ms) was significantly shorter than that of NCM (56.7 ms), with a sensitivity of 100% and a specificity of 89.5% at a threshold of 45.0 ms. A minimum of 10 randomly selected bursts were sufficient for reliable diagnostic accuracy. CONCLUSION: The burst duration seems a valuable supportive diagnostic criterion for distinguishing CM and NCM. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Tremor after solid organ transplantation: Results from the TransplantLines Biobank and Cohort Study.

BACKGROUND AND PURPOSE: Tremor is a frequent complaint of solid organ transplant recipients. We report on the largest population investigated with clinical neurophysiological methods. Our aim is to objectively establish the tremor prevalence and syndrome in the largest population of solid organ transplant recipients. METHODS: Tremor was measured in heart, kidney, liver, and lung recipients, using accelerometers during rest, postural, and weight-loaded conditions. The 95th percentile of healthy kidney donors' tremor amplitude was used as the cutoff to determine the presence of tremor in transplant recipients. Tremor frequency, frequency variability, and effect of loading were used to investigate enhanced physiological tremor as the likely tremor syndrome. Impact on activities of daily life was assessed, and correlations with tacrolimus blood levels were investigated. RESULTS: Tremor was present in 52% of 246 transplant recipients, typically in postural positions. Mean tremor frequency was 6.1 (±2.0) Hz; mean tremor variability was 2.6 (±1.8) Hz. A frequency decrease upon loading was found in 83% of patients with tremor. Sixty-five percent of patients met formal clinical neurophysiological criteria for enhanced physiological tremor. Tremor-related impairment was present in 55% and correlated with tremor amplitude (ρ = 0.23, p ≤ 0.001). In a binominal regression analysis, tacrolimus blood levels were independently associated with tremor prevalence (p = 0.009). CONCLUSIONS: More than half of solid organ transplant recipients experience a tremor that best fits the syndrome of enhanced physiological tremor. This is the first objective study on tremor that has established a better understanding of the neurophysiological mechanisms of tremor in a large population of solid organ transplant recipients.

Diagnostic value of transcranial doppler to predict delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage : To predict delayed cerebral ischemia.

BACKGROUND: Transcranial Doppler (TCD) is a technique to assess blood flow velocity in the cerebral arteries. TCD is frequently used to monitor aneurysmal subarachnoid hemorrhage (aSAH) patients. This study compares TCD-criteria for vasospasm and its association with Delayed Cerebral Ischemia (DCI). An overall score based on flow velocities of various intracranial arteries was developed and evaluated. METHODS: A retrospective diagnostic accuracy study was conducted between 1998 and 2017 with 621 patients included. Mean flow velocity (MFV) of the cerebral artery was measured between 2-5 days and between 6-9 days after ictus. Cutoff values from the literature, new cutoff values, and a new composite score (Combined Severity Score) were used to predict DCI. Sensitivity, specificity, and area under the curve (AUC) were determined, and logistic regression analysis was performed. RESULTS: The Combined Severity Score showed an AUC 0.64 (95%CI 0.56-.71) at days 2-5, with sensitivity 0.53 and specificity 0.74. The Combined Severity Score had an adjusted Odds Ratio of 3.41 (95CI 1.86-6.32) for DCI. MCA-measurements yielded the highest AUC to detect DCI at day 2-5: AUC 0.65 (95%CI 0.58-0.73). Optimal cutoff MFV of 83 cm/s for MCA resulted in sensitivity 0.73 and specificity 0.50 at days 2-5. CONCLUSION: TCD-monitoring of aSAH patients may be a valuable strategy for DCI risk stratification. Lower cutoff values can be used in the early phase after the ictus (day 2-5) than are commonly used now. The Combined Severity Score incorporating all major cerebral arteries may provide a meaningful contribution to interpreting TCD measurements.

Tremor, Daily Functioning, and Health-Related Quality of Life in Solid Organ Transplant Recipients.

Solid organ transplant recipients (SOTR) frequently report tremor. Data concerning tremor-related impairment and its potential impact on health-related quality of life (HRQoL) are lacking. This cross-sectional study assesses impact of tremor on activities of daily living and HRQoL using validated questionnaires among SOTR enrolled in the TransplantLines Biobank and Cohort Study. We included 689 SOTR (38.5% female, mean [±SD] age 58 [±14] years) at median [interquartile range] 3 [1-9] years after transplantation, of which 287 (41.7%) reported mild or severe tremor. In multinomial logistic regression analyses, whole blood tacrolimus trough concentration was an independent determinant of mild tremor (OR per µg/L increase: 1.11, 95% CI: 1.02 to 1.21, p = 0.019). Furthermore, in linear regression analyses, severe tremor was strongly and independently associated with lower physical and mental HRQoL (ß = -16.10, 95% CI: -22.23 to -9.98, p < 0.001 and ß = -12.68, 95% CI: -18.23 to -7.14, p < 0.001 resp.). SOTR frequently report tremor-related impairment of activities of daily living. Tacrolimus trough concentrations appeared as a main determinant of tremor among SOTR. The strong and independent association of tremor-related impairment with lower HRQoL warrants further studies into the effects of tacrolimus on tremor. Clinical Trial Registration: ClinicalTrials.gov, Identifier NCT03272841.

Instrumented Gait Classification Using Meaningful Features in Patients with Impaired Coordination.

Early onset ataxia (EOA) and developmental coordination disorder (DCD) both affect cerebellar functioning in children, making the clinical distinction challenging. We here aim to derive meaningful features from quantitative SARA-gait data (i.e., the gait test of the scale for the assessment and rating of ataxia (SARA)) to classify EOA and DCD patients and typically developing (CTRL) children with better explainability than previous classification approaches. We collected data from 18 EOA, 14 DCD and 29 CTRL children, while executing both SARA gait tests. Inertial measurement units were used to acquire movement data, and a gait model was employed to derive meaningful features. We used a random forest classifier on 36 extracted features, leave-one-out-cross-validation and a synthetic oversampling technique to distinguish between the three groups. Classification accuracy, probabilities of classification and feature relevance were obtained. The mean classification accuracy was 62.9% for EOA, 85.5% for DCD and 94.5% for CTRL participants. Overall, the random forest algorithm correctly classified 82.0% of the participants, which was slightly better than clinical assessment (73.0%). The classification resulted in a mean precision of 0.78, mean recall of 0.70 and mean F1 score of 0.74. The most relevant features were related to the range of the hip flexion-extension angle for gait, and to movement variability for tandem gait. Our results suggest that classification, employing features representing different aspects of movement during gait and tandem gait, may provide an insightful tool for the differential diagnoses of EOA, DCD and typically developing children.

The predictive value of the CTA Vasospasm Score on delayed cerebral ischaemia and functional outcome after aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Delayed cerebral ischaemia (DCI) is a severe complication of aneurysmal subarachnoid hemorrhage that can significantly impact clinical outcome. Cerebral vasospasm is part of the pathophysiology of DCI and therefore a computed tomography angiography (CTA) Vasospasm Score was developed and an exploration was carried out of whether this score predicts DCI and subsequent poor outcome after aneurysmal subarachnoid hemorrhage. METHODS: The CTA Vasospasm Score sums the degree of angiographic cerebral vasospasm of 17 intradural arterial segments. The score ranges from 0 to 34 with a higher score reflecting more severe vasospasm. Outcome measures were cerebral infarction due to DCI (CI-DCI), radiological and clinical DCI, and unfavorable functional outcome defined as a modified Rankin Scale >2 at 6 months. Receiver operating characteristic analyses were used to assess predictive value and to determine optimal cut-off scores. Inter-rater reliability was evaluated by Cohen's kappa coefficient. RESULTS: This study included 59 patients. CI-DCI occurred in eight patients (14%), DCI in 14 patients (24%) and unfavorable outcome in 12 patients (20%). Median CTA Vasospasm Scores were higher in patients with (CI-)DCI and poor outcome. Receiver operating characteristic analysis revealed the highest area under the curve on day 5: CI-DCI 0.89 (95% confidence interval [CI] 0.79-0.99), DCI 0.68 (95% CI 0.50-0.87) and functional outcome 0.74 (95% CI 0.57-0.91). Cohen's kappa between the two raters was moderate to substantial (0.57-0.63). CONCLUSIONS: This study demonstrates that the CTA Vasospasm Score on day 5 can reliably identify patients with a high risk of developing (CI-)DCI and unfavorable outcome.

Cerebral autoregulation assessed by near-infrared spectroscopy: validation using transcranial Doppler in patients with controlled hypertension, cognitive impairment and controls.

PURPOSE: Cerebral autoregulation (CA) aims to attenuate the effects of blood pressure variation on cerebral blood flow. This study assessed the criterion validity of CA derived from near-infrared spectroscopy (NIRS) as an alternative for Transcranial Doppler (TCD). METHODS: Measurements of continuous blood pressure (BP), oxygenated hemoglobin (O2Hb) using NIRS and cerebral blood flow velocity (CBFV) using TCD (gold standard) were performed in 82 controls, 27 patients with hypertension and 94 cognitively impaired patients during supine rest (all individuals) and repeated sit to stand transitions (cognitively impaired patients). The BP-CBFV and BP-O2Hb transfer function phase shifts (TFφ) were computed as CA measures. Spearman correlations (ρ) and Bland Altman limits of agreement (BAloa) between NIRS- and TCD-derived CA measures were computed. BAloa separation < 50° was considered a high absolute agreement. RESULTS: NIRS- and TCD-derived CA estimates were significantly correlated during supine rest (ρ = 0.22-0.30, N = 111-120) and repeated sit-to-stand transitions (ρ = 0.46-0.61, N = 19-32). BAloa separation ranged between 87° and 112° (supine rest) and 65°-77° (repeated sit to stand transitions). CONCLUSION: Criterion validity of NIRS-derived CA measures allows for comparison between groups but was insufficient for clinical application in individuals.

Systematic clinical approach for diagnosing upper limb tremor.

Tremor is the most common movement disorder worldwide, but diagnosis is challenging. In 2018, the task force on tremor of the International Parkinson and Movement Disorder Society published a consensus statement that proposes a tremor classification along two independent axes: a clinical tremor syndrome and its underlying aetiology. In line with this statement, we here propose a stepwise diagnostic approach that leads to the correct clinical and aetiological classification of upper limb tremor. We also describe the typical clinical signs of each clinical tremor syndrome. A key feature of our algorithm is the distinction between isolated and combined tremor syndromes, in which tremor is accompanied by bradykinesia, cerebellar signs, dystonia, peripheral neuropathy or brainstem signs. This distinction subsequently informs the selection of appropriate diagnostic tests, such as neurophysiology, laboratory testing, structural and dopaminergic imaging and genetic testing. We highlight treatable metabolic causes of tremor, as well as drugs and toxins that can provoke tremor. The stepwise approach facilitates appropriate diagnostic testing and avoids unnecessary investigations. We expect that the approach offered in this article will reduce diagnostic uncertainty and increase the diagnostic yield in patients with tremor.

Hemodialysis Induces an Acute Decline in Cerebral Blood Flow in Elderly Patients.

The initiation of hemodialysis is associated with an accelerated decline of cognitive function and an increased incidence of cerebrovascular accidents and white matter lesions. Investigators have hypothesized that the repetitive circulatory stress of hemodialysis induces ischemic cerebral injury, but the mechanism is unclear. We studied the acute effect of conventional hemodialysis on cerebral blood flow (CBF), measured by [15O]H2O positron emission tomography-computed tomography (PET-CT). During a single hemodialysis session, three [15O]H2O PET-CT scans were performed: before, early after the start of, and at the end of hemodialysis. We used linear mixed models to study global and regional CBF change during hemodialysis. Twelve patients aged ≥65 years (five women, seven men), with a median dialysis vintage of 46 months, completed the study. Mean (±SD) arterial BP declined from 101±11 mm Hg before hemodialysis to 93±17 mm Hg at the end of hemodialysis. From before the start to the end of hemodialysis, global CBF declined significantly by 10%±15%, from a mean of 34.5 to 30.5 ml/100g per minute (difference, -4.1 ml/100 g per minute; 95% confidence interval, -7.3 to -0.9 ml/100 g per minute; P=0.03). CBF decline (20%) was symptomatic in one patient. Regional CBF declined in all volumes of interest, including the frontal, parietal, temporal, and occipital lobes; cerebellum; and thalamus. Higher tympanic temperature, ultrafiltration volume, ultrafiltration rate, and pH significantly associated with lower CBF. Thus, conventional hemodialysis induces a significant reduction in global and regional CBF in elderly patients. Repetitive intradialytic decreases in CBF may be one mechanism by which hemodialysis induces cerebral ischemic injury.

Progressive myoclonus ataxia: Time for a new definition?

BACKGROUND: The clinical demarcation of the syndrome progressive myoclonus ataxia is unclear, leading to a lack of recognition and difficult differentiation from other neurological syndromes. OBJECTIVES: The objective of this study was to apply a refined definition of progressive myoclonus ataxia and describe the clinical characteristics in patients with progressive myoclonus ataxia and with isolated cortical myoclonus. METHODS: A retro- and prospective analysis was performed in our tertiary referral center between 1994 and 2014. Inclusion criteria for progressive myoclonus ataxia patients were the presence of myoclonus and ataxia with or without infrequent (all types, treatment responsive) epileptic seizures. Inclusion criteria for isolated cortical myoclonus was the presence of isolated cortical myoclonus. Clinical and electrophysiological characteristics data were systematically scored. RESULTS: A total of 14 progressive myoclonus ataxia patients (males, 7; females, 7), median age 14.5 years, and 8 isolated cortical myoclonus patients (males, 2; females, 6), median age 23.5 years, were identified. In 93% of the progressive myoclonus ataxia patients, ataxia started first (median 2 years) followed by myoclonus (4 years) and finally infrequent epilepsy (9.3 years), with a progressive course in 93%. In 64% of the progressive myoclonus ataxia patients, a genetic underlying etiology was identified, including 3 not earlier reported causative progressive myoclonus ataxia genes. In isolated cortical myoclonus patients, myoclonus started at (median) 12 years with progression over time in 63% and a single epileptic seizure in 1 patient. No genetic causes were identified. CONCLUSION: Using a refined definition, we could create a rather homogenous progressive myoclonus ataxia group. Patients with isolated cortical myoclonus have a different course and do not appear to evolve in progressive myoclonus ataxia. The refined progressive myoclonus ataxia definition is a successful first step toward creating a separate syndrome for both clinical practice and future genetic research. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Visualisation of the 'Optimal Cerebral Perfusion' Landscape in Severe Traumatic Brain Injury Patients.

OBJECTIVE: An 'optimal' cerebral perfusion pressure (CPPopt) can be defined as the point on the CPP scale corresponding to the greatest autoregulatory capacity. This can be established by examining the pressure reactivity index PRx-CPP relationship, which is approximately U-shaped but suffers from noise and missing data. In this paper, we present a method for plotting the whole PRx-CPP relationship curve against time in the form of a colour-coded map depicting the 'landscape' of that relationship extending back for several hours and to display this robustly at the bedside.This is a short version of a full paper recently published in Critical Care Medicine (2016) containing some new insights and details of a novel bedside implementation based on a presentation during Intracranial Pressure 2016 Symposium in Boston. METHODS: Recordings from routine monitoring of traumatic brain injury patients were processed using ICM+. Time-averaged means for arterial blood pressure, intracranial pressure, cerebral perfusion pressure (CPP) and pressure reactivity index (PRx) were calculated and stored with time resolution of 1 min. ICM+ functions have been extended to include not just an algorithm of automatic calculation of CPPopt but also the 'CPPopt landscape' chart. RESULTS: Examining the 'CPPopt landscape' allows the clinician to differentiate periods where the autoregulatory range is narrow and needs to be targeted from periods when the patient is generally haemodynamically stable, allowing for more relaxed CPP management. This information would not have been conveyed using the original visualisation approaches. CONCLUSIONS: We describe here a natural extension to the concept of autoregulatory assessment, providing the retrospective 'landscape' of the PRx-CPP relationship extending over the past several hours. We have incorporated such visualisation techniques online in ICM+. The proposed visualisation may facilitate clinical evaluation and use of autoregulation-guided therapy.

Enhanced Visualization of Optimal Cerebral Perfusion Pressure Over Time to Support Clinical Decision Making.

OBJECTIVE: Cerebrovascular reactivity can provide a continuously updated individualized target for management of cerebral perfusion pressure, termed optimal cerebral perfusion pressure. The objective of this project was to find a way of improving the optimal cerebral perfusion pressure methodology by introducing a new visualization method. DATA SOURCES: Four severe traumatic brain injury patients with intracranial pressure monitoring. DATA EXTRACTION: Data were collected and pre-processed using ICM+ software. DATA SYNTHESIS: Sequential optimal cerebral perfusion pressure curves were used to create a color-coded maps of autoregulation - cerebral perfusion pressure relationship evolution over time. CONCLUSIONS: The visualization method addresses some of the main drawbacks of the original methodology and might bring the potential for its clinical application closer.

Observation of Autoregulation Indices During Ventricular CSF Drainage After Aneurysmal Subarachnoid Hemorrhage: A Pilot Study.

BACKGROUND: Cerebral autoregulation is increasingly recognized as a factor that requires evaluation when managing poor grade aneurysmal subarachnoidal hemorrhage (aSAH) patients. In this single center pilot study, we investigated whether intraventricular intracranial pressure (ICP) derived when extraventricular drain (EVD) is open can be used to calculate dynamic autoregulation estimates in ICU aSAH patients. METHODS: Ten patients with the diagnosis of aSAH as confirmed by computed tomography (CT) and CT-angiography were enrolled. ICP was monitored via a transducer connected to the most proximal side exit of the EVD catheter. From at least 30 min periods of brain monitoring before, during, and after temporarily EVD closure, commonly used indexes of dynamic cerebral autoregulation were calculated. RESULTS: Preserved pulsatile ICP signals were seen with open EVD. There were no significant changes in parameters describing cerebral autoregulation between EVD open and closed conditions. Power spectra of ABP and ICP showed no significant changes for the selected frequency ranges. There was a small significant increase in absolute ICP [2.4 (3.8) mmHg, p < 0.001] upon short-term EVD closure. Cerebral spinal reserve capacity (RAP index) worsened significantly by short-term EVD closure. CONCLUSIONS: Due to preserved slow fluctuations in the ICP signal, an open EVD system can be used to calculate dynamic autoregulation indices in aSAH patients requiring intensive care monitoring with the pressure measurement from the most proximal part of drain. If these results are confirmed in larger study, this technique can open the way for investigating the role of autoregulation disturbance in aSAH patients.

Ramsay Hunt syndrome: clinical characterization of progressive myoclonus ataxia caused by GOSR2 mutation.

BACKGROUND: Ramsay Hunt syndrome (progressive myoclonus ataxia) is a descriptive diagnosis characterized by myoclonus, ataxia, and infrequent seizures. Often the etiology cannot be determined. Recently, a mutation in the GOSR2 gene (c.430G>T, p.Gly144Trp) was reported in 6 patients with childhood-onset progressive ataxia and myoclonus. METHODS: We evaluated 5 patients with cortical myoclonus, ataxia, and areflexia. RESULTS: All 5 patients had the same homozygous mutation in GOSR2. Here we present their clinical and neurophysiological data. Our patients (aged 7-26 years) all originated from the northern Netherlands and showed a remarkably homogeneous phenotype. Myoclonus and ataxia were relentlessly progressive over the years. Electromyography revealed signs of sensory neuronopathy or anterior horn cell involvement, or both, in all patients with absent reflexes. CONCLUSIONS: Based on the presented phenotype, we would advise movement disorder specialists to consider mutation analysis of GOSR2 in patients with Ramsay Hunt syndrome, especially when they also have areflexia.

Modulation of cerebral blood flow with transcutaneous electrical neurostimulation (TENS) in patients with cerebral vasospasm after subarachnoid hemorrhage.

OBJECTIVES: Transcutaneous electrical neurostimulation (TENS) and spinal cord stimulation have been shown to increase peripheral and cerebral blood flow. We postulate that certain pathological conditions attenuate cerebral autoregulation, which may result in a relative increase of the importance of neurogenic regulation of cerebral blood flow, which could be decreased by electrical modulation. We therefore assess the effects of TENS on cerebral blood flow velocities (CBFVs) and cerebral saturation in patients with cerebral vasospasm after subarachnoid hemorrhage (SAH). MATERIALS AND METHODS: Cervical TENS was applied in 10 SAH patients with transcranial Doppler (TCD)-proven cerebral vasospasm. Measurements included plethysmography, near-infrared spectroscopy, capnography, and CBFVs by TCD. After determining the optimal frequency and current, patients were treated with cervical TENS for two periods of three days, with a pause of one day in between. RESULTS: The TENS electrodes were not always tolerated by the patients. Higher frequencies demonstrated the most prominent combined effects. ETCO2 was 0.19% lower with TENS off than with TENS on (p = 0.05). Mean arterial blood pressure and pulse were not significantly different over time. CBFV in MCA was decreased (p = 0.07) while cerebral oxygen saturation was increased (p = 0.01) after the use of TENS. CONCLUSIONS: Our data suggest improved cerebral blood flow when using cervical TENS in patients with cerebral vasospasm. Several factors could have attenuated the effects: the electrodes were poorly tolerated, ETCO2 increased during TENS, few vessels showed prolonged vasospasm, and overall flow velocities were low. Still, an on-off effect of TENS over time was detected.

Haemosync: A synchronisation algorithm for multimodal haemodynamic signals.

BACKGROUND: Synchronous acquisition of haemodynamic signals is crucial for their multimodal analysis, such as dynamic cerebral autoregulation (DCA) analysis of arterial blood pressure (ABP) and transcranial Doppler (TCD)-derived cerebral blood velocity (CBv). Several technical problems can, however, lead to (varying) time-shifts between the different signals. These can be difficult to recognise and can strongly influence the multimodal analysis results. METHODS: We have developed a multistep, cross-correlation-based time-shift detection and synchronisation algorithm for multimodal pulsatile haemodynamic signals. We have developed the algorithm using ABP and CBv measurements from a dataset that contained combinations of several time-shifts. We validated the algorithm on an external dataset with time-shifts. We additionally quantitatively validated the algorithm's performance on a dataset with artificially added time-shifts, consisting of sample clock differences ranging from -0.2 to 0.2 s/min and sudden time-shifts between -4 and 4 s. The influence of superimposed noise and variation in waveform morphology on the time-shift estimation was quantified, and their influence on DCA-indices was determined. RESULTS: The instantaneous median absolute error (MedAE) between the artificially added time-shifts and the estimated time-shifts was 12 ms (median, IQR 12-12, range 11-14 ms) for drifts between -0.1 and 0.1 s/min and sudden time-shifts between -4 and 4 s. For drifts above 0.1 s/min, MedAE was higher (median 753, IQR 19 - 766, range 13 - 772 ms). When a certainty threshold was included (peak cross-correlation > 0.9), MedAE for all drifts-shift combinations decreased to 12 ms, with smaller variability (IQR 12 - 13, range 8 - 22 ms, p < 0.001). The time-shift estimation is robust to noise, as the MedAE was similar for superimposed white noise with variance equal to the signal variance. After time-shift correction, DCA-indices were similar to the original, non-time-shifted signals. Phase shift differed by 0.17° (median, IQR 0.13-0.2°, range 0.0038-1.1°) and 0.54° (median, IQR 0.23-1.7°, range 0.0088-5.6°) for the very low frequency and low frequency ranges, respectively. DISCUSSION: This algorithm allows visually interpretable detection and accurate correction of time-shifts between pulsatile haemodynamic signals (ABP and CBv).

A Novel Accelerometry Method to Perioperatively Quantify Essential Tremor Based on Fahn-Tolosa-Marin Criteria.

The disease status, progression, and treatment effect of essential tremor (ET) patients are currently assessed with clinical scores, such as the Fahn-Tolosa-Marin Clinical Rating Scale for Tremor (FTM). The use of objective and rater-independent monitoring of tremors may improve clinical care for patients with ET. Therefore, the focus of this study is to develop an objective accelerometry-based method to quantify ET, based on FTM criteria. Thirteen patients with ET and thirteen matched healthy participants underwent FTM tests to rate tremor severity, paired with tri-axial accelerometric measurements at the index fingers. Analogue FTM assessments were performed by four independent raters based on video recordings. Quantitative measures were derived from the accelerometric data, e.g., the area under the curve of power in the 4-8 Hz frequency band (AUCP) and maximal tremor amplitude. As such, accelerometric tremor scores were computed, using thresholds based on healthy measurements and FTM criteria. Agreement between accelerometric and clinical FTM scores was analyzed with Cohen's kappa coefficient. It was assessed whether there was a relationship between mean FTM scores and the natural logarithm (ln) of the accelerometric outcome measures using linear regression. The agreement between accelerometric and FTM scores was substantial for resting and intention tremor tests (≥72.7%). However, the agreement between accelerometric postural tremor data and clinical FTM ratings (κ = 0.459) was low, although their logarithmic (ln) relationship was substantial (R2 ≥ 0.724). Accelerometric test-retest reliability was good to excellent (ICC ≥ 0.753). This pilot study shows that tremors can be quantified with accelerometry, using healthy thresholds and FTM criteria. The test-retest reliability of the accelerometric tremor scoring algorithm indicates that our low-cost accelerometry-based approach is a promising one. The proposed easy-to-use technology could diminish the rater dependency of FTM scores and enable physicians to monitor ET patients more objectively in clinical, intraoperative, and home settings.