Clinical outcomes among initial survivors of cryptogenic new-onset refractory status epilepsy (NORSE).

OBJECTIVE: New-onset refractory status epilepticus (NORSE) is a rare but severe clinical syndrome. Despite rigorous evaluation, the underlying cause is unknown in 30%-50% of patients and treatment strategies are largely empirical. The aim of this study was to describe clinical outcomes in a cohort of well-phenotyped, thoroughly investigated patients who survived the initial phase of cryptogenic NORSE managed in specialist centers. METHODS: Well-characterized cases of cryptogenic NORSE were identified through the EPIGEN and Critical Care EEG Monitoring Research Consortia (CCEMRC) during the period 2005-2019. Treating epileptologists reported on post-NORSE survival rates and sequelae in patients after discharge from hospital. Among survivors >6 months post-discharge, we report the rates and severity of active epilepsy, global disability, vocational, and global cognitive and mental health outcomes. We attempt to identify determinants of outcome. RESULTS: Among 48 patients who survived the acute phase of NORSE to the point of discharge from hospital, 9 had died at last follow-up, of whom 7 died within 6 months of discharge from the tertiary care center. The remaining 39 patients had high rates of active epilepsy as well as vocational, cognitive, and psychiatric comorbidities. The epilepsy was usually multifocal and typically drug resistant. Only a minority of patients had a good functional outcome. Therapeutic interventions were heterogenous during the acute phase of the illness. There was no clear relationship between the nature of treatment and clinical outcomes. SIGNIFICANCE: Among survivors of cryptogenic NORSE, longer-term outcomes in most patients were life altering and often catastrophic. Treatment remains empirical and variable. There is a pressing need to understand the etiology of cryptogenic NORSE and to develop tailored treatment strategies.

New-onset super refractory status epilepticus: A case-series.

INTRODUCTION: Literature on New-Onset Refractory Status Epilepticus (NORSE) is scarce and management is guided mainly by retrospective reports, short case series or expert opinions. We aimed to add to the pool of the available data by retrospectively reviewing seven cases of NORSE cases admitted to our hospital over the last five years between January 2014 and March 2019. METHODS: Fully anonymised data from medical charts, EEG reports, imaging reports, laboratory test results, types of antiepileptic medications, intravenous anaesthetic therapy, and immune therapies received was collected, along with response to treatment, length of hospital stay and outcome at discharge. RESULTS: The mean age was 43.5 ±â€¯23.8 years (range 18-75) and three patients were females. Prodromal symptoms consisted mainly of fever (4/7), headache (4/7) and self terminating seizures (7/7), before presenting with status epilepticus. Initial imaging findings were abnormal in 3/7 and CSF analysis in 3/7. All patients underwent intermittent EEG recordings, mainly for titration or tapering of the anaesthetic agents, with the initial goal of achieving burst suppression and cessation of electrographic seizures. Our index case spent the longest time in therapeutic burst suppression (102 days) and remained on thiopentone for 214 days. The mean duration of NICU stay was 88 ±â€¯85.4 days (range 4-225 days) while the mean duration of hospital stay was 113.8 ±â€¯111.2 days (range 17-292). CONCLUSIONS: The management of patients with NORSE remains challenging, often requiring multiple intravenous anaesthetic treatments, leading to complicated and prolonged hospital and intensive care unit stays but good outcome remains possible.

A pragmatic approach to intravenous anaesthetics and electroencephalographic endpoints for the treatment of refractory and super-refractory status epilepticus in critical care.

Status epilepticus is a common neurological emergency, with overall mortality around 20%. Over half of cases are first time presentations of seizures. The pathological process by which spontaneous seizures are generated arises from an imbalance in excitatory and inhibitory neuronal networks, which if unchecked, can result in alterations in intracellular signalling pathways and electrolyte shifts, which bring about changes in the blood brain barrier, neuronal cell death and eventually cerebral atrophy. This narrative review focusses on the treatment of status epilepticus in adults. Anaesthetic agents interrupt neuronal activity by enhancing inhibitory or decreasing excitatory transmission, primarily via GABA and NMDA receptors. Intravenous anaesthetic agents are commonly used as second or third line drugs in the treatment of refractory status epilepticus, but the optimal timing and choice of anaesthetic drug has not yet been established by high quality evidence. Titration of antiepileptic and anaesthetic drugs in critically ill patients presents a particular challenge, due to alterations in drug absorbtion and metabolism as well as changes in drug distrubution, which arise from fluid shifts and altered protein binding. Furthermore, side effects associated with prolonged infusions of anaesthetic drugs can lead to multi-organ dysfunction and a need for critical care support. Electroencelography can identify patterns of burst suppression, which may be a target to guide weaning of intravenous therapy. Continuous elctroencephalography has the potential to directly impact clinical care, but despite its utility, major barriers exist which have limited its widespread use in clinical practice. A flow chart outlining the timing and dosage of anaesthetic agents used at our institution is provided.

Relationship between anti-acetylcholine receptor antibody titres and severity of myasthenia gravis.

OBJECTIVE: To study the relationship of anti acetylycholine receptor antibody (AchR-Ab) titres with the demographic profile and severity of myasthenia gravis (MG). METHODS: This prospective study was carried out on inpatients and outpatients at the Department of Neurology at Pakistan Institute of Medical Sciences, Islamabad. Seropositive cases of myasthenia gravis were collected and were classified as having low AchR-Ab titres (< 50 nmol/L) and high AchR-Ab titres (> 50 nmol/L). The comparison of these patients was done using the following parameters: sex, age, clinical presentations, severity of the disease, repeated nerve stimulation test, prostigmine test, the association with thymus status, other autoimmune diseases, and therapeutic outcome. RESULTS: Out of a total 71 seropositive MG patients enrolled in the study, forty one (57.7%) patients had low titres and thirty (42.2%) had high titres. Their mean age was 33.18 +/- 12.99 years (range 13-70) and thirty eight of them were females. The AchR-Ab titers were higher in the younger age group and in women than in men, however, the results were statistically insignificant. The most common presenting symptoms were ocular (91%), followed by generalized weakness with easy fatiguability (57%) and bulbar weakness (46.4%). Majority of the patients at the time of presentation were in Osserman's stage III (43%); while 26% and 19.7% were in stage IIA and IIB respectively. There was no association between the AchR-Ab titers and clinical grades of Osserman's classification. CONCLUSION: Serum concentration of anti acetylcholine receptor antibodies do not relate with the clinical severity of myasthenia gravis.

Chest radiographic findings in neurotuberculosis without pulmonary signs and symptoms.

OBJECTIVE: To determine the chest radiographic findings in patients of adult neurotuberculosis, with no pulmonary signs and symptoms. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Department of Neurology, Pakistan Institute of Medical Sciences, Islamabad, Pakistan, from January 2004 to January 2006. PATIENTS AND METHODS: A total of 100 patients fulfilling pre-defined criteria of neurotuberculosis were included. Chest radiographic (CXR) evidence of pulmonary TB was looked for in those patients and its frequency, pattern and association with the clinical grades at presentation was determined by using Chi-square test. RESULTS: Out of the 100 patients of neurotuberculosis, with no clinical evidence of pulmonary TB, radiographic evidence of pulmonary TB was seen in only 30% patients. The predominant patterns on CXR were apical infiltration (26.6%), miliary mottling (20%) and hilar enlargement (16.6%). Positive CXR was found in 16.7% patients in clinical grade I and 40% and 43.3% in patients in grade II and III respectively. There was a strong association of grade II and grade III with positive chest radiographic findings (p= 0.03). CONCLUSION: Patients of neurotuberculosis may have chest radiographic evidence of pulmonary TB even in the absence of pulmonary signs and symptoms at presentation. There is a strong association of clinical grade II and grade III with positive chest radiographic findings.

Treating infected diabetic wounds with superoxidized water as anti-septic agent : a preliminary experience.

OBJECTIVE: To evaluate the effectiveness of superoxidized water (MicrocynTM) in diabetic patients with different wounds. STUDY DESIGN: Single-centre single blinded randomized controlled trial. PLACE AND DURATION OF STUDY: Department of General Surgery, Orthopaedics and General Medicine at Pakistan Institute of Medical Sciences, Islamabad, from April to June 2006. PATIENTS AND METHODS: One hundred known diabetic patients were enrolled. Half were randomized to the intervention group (those whose wounds were managed with superoxidized water) and half to the control group (whose wounds were treated with normal saline) using a table of random numbers. The two groups were matched for age, gender, duration of diabetes and category of wound. All patients received appropriate surgical treatment for their wounds as required. Local wound treatment was carried out daily using superoxidized water soaked gauzes on twice daily basis in the intervention group and normal saline in the control group. The treatment was continued until wound healing. The main outcome measures were duration of hospital stay, downgrading of the wound category, wound healing time and need for interventions such as amputation. RESULTS: Statistically significant differences were found in favour of the superoxidized water group with respect to duration of hospital stay, downgrading of the wound category and wound healing time. CONCLUSION: Although the initial results of employing superoxidized water for the management of infected diabetic wounds are encouraging, further multicentre clinical trials are warranted before this antiseptic is recommended for general use. It may offer an economical alternative to other expensive antiseptics with positive impact on the prevailing infection rates, patient outcomes and patient satisfaction.

LGI1-antibody encephalitis is characterised by frequent, multifocal clinical and subclinical seizures.

PURPOSE: To describe clinical and electrographic characteristics of seizures LGI1-antibody encephalitis, and their correlations with two-year outcomes. METHODS: Video-electroencephalography recordings were performed on a cohort of 16 consecutive patients with LGI1-antibodies from two UK neuroscience-centers over five-years. RESULTS: From 14 of 16 patients (13 males; age-range 53-92years), 86 faciobrachial dystonic seizures were recorded at a median frequency of 0.4 per hour (range 0.1-9.8), and ictal EEG changes accompanied 5/86 events. In addition, 11/16 patients showed 53 other seizures - subclinical (n=18), motor (n=16), or sensory (n=19) - at a median of 0.1 per hour (range 0.1-2) associated with temporal and frontal discharges. The sensory events were most commonly thermal sensations or body-shuddering, and the motor events were frequently automatisms or vocalisations. Furthermore, multifocal interictal epileptiform discharges, from temporal, frontal and parietal regions, and interictal slow-wave activity were observed in 25% and 69% of patients, respectively. Higher observed seizure frequency correlated with poorer functional recovery at two-years (p=0.001). CONCLUSIONS: Multiple frequent seizure semiologies, in addition to numerous subclinical seizures and interictal epileptiform discharges, are hallmarks of LGI1-antibody encephalitis. High overall seizure frequency may predict more limited long-term recovery. These observations should encourage closer monitoring and proactive treatment of seizure activity in these patients.