Antiseizure Medication Withdrawal, Risk of Epilepsy, and Longterm EEG Trends in Acute Symptomatic Seizures or Epileptic EEG Patterns.

Background and Objectives: Patients with acute symptomatic seizures (ASyS) and acute epileptiform findings on EEG are common. They are often prescribed long-term antiseizure medications (ASMs); it is unknown whether or when this is necessary. Primary outcome was late unprovoked seizure occurrence and association with ASM taper. The secondary outcome was EEG pattern evolution over time. Methods: This is a retrospective cohort study of patients from 2015 to 2021 with ASyS (clinical or electrographic) and/or epileptiform findings on index hospitalization EEGs who were discharged on ASMs and had subsequent follow-up including an outpatient EEG at Yale New Haven Hospital. All patients were seen in our postacute symptomatic seizure (PASS) clinic after hospital discharge. We also developed a simple predictive score, Epilepsy-PASS (EPI-PASS), using variables independently associated with seizure recurrence based on stepwise regression; each of the 3 identified variables was assigned a score of 0 (absent) or 1 (present), for a total score of 0-3. Results: Of 190 patients screened, 58 were excluded, leaving a final cohort of 112 patients. Twenty-four percent (27/112) patients developed a late unprovoked seizure (i.e., epilepsy). Independent predictors of epilepsy were persistence of epileptiform abnormalities on follow-up EEGs [56% developed epilepsy vs 19% without, 0.002, OR 7.18 (1.36-37.88)], clinical ASyS [32% vs 13%, p = 0.002, OR 7.45 (2.31-54.36)], and cortical involvement on imaging [40% vs 11%, p = 0.003, OR 7.63 (1.96-29.58)]. None of the 23 patients with none of these predictors (0 points on EPI-PASS) developed epilepsy, vs 13% with 1 predictor (EPI-PASS = 1) and 46% with 2 or 3 predictors (EPI-PASS = 2-3) at 1-year follow-up. ASM taper was not associated with seizure recurrence. Abnormal EEG findings in the index hospitalization usually resolved [54/69 (78%) patients] on subsequent EEGs. Discussion: Most patients with clinical ASyS or acute epileptiform EEG findings do not require long-term ASMs. Index hospitalization EEG findings usually resolve, but if they do not, there is a >50% chance of developing epilepsy. Other predictors of epilepsy are cortical involvement on imaging and clinical ASyS. A simple 4-point scale using these 3 predictors (EPI-PASS) may help predict the risk of developing epilepsy but requires independent validation.

Rickettsial Cerebellitis: A Rare Neurological Manifestation.

Scrub typhus is a vector-borne disease caused by gram-negative bacilli, Orientia tsutsugamushi. The vector of scrub typhus is the mite. The clinical manifestations often present with either a simple fever or life-threatening multi-organ dysfunction. Neurological manifestations also vary, and the incidence of neurological manifestations is unknown. Cerebellitis is one of the rare neurological manifestations associated with scrub typhus. In this case report, we present the case of a 35-year-old man who tested positive for scrub typhus (IgM enzyme-linked immunosorbent assay (ELISA) blood test) with a history of fever and cerebellar signs and symptoms. He was managed with antibacterial agents and made a good recovery.

The Significance of LRDA With Bilateral Involvement Compared With GRDA on EEG in Critically Ill Patients.

PURPOSE: Lateralized rhythmic delta activity (LRDA) is highly associated with seizures but generalized rhythmic delta activity (GRDA; symmetric by definition) has no known seizure association. A subset of LRDA includes patterns that are "bilateral asymmetric LRDA" (LRDA-ba), falling between purely unilateral LRDA and GRDA. The significance of this finding has not been previously addressed. METHODS: Clinical, EEG, and imaging findings were reviewed in all patients with >6 hours of continuous EEG and LRDA-ba between 2014 and 2019. They were compared with a control group of patients with GRDA, matched 1:1 for prevalence, duration, and frequency of the predominant rhythmic pattern. RESULTS: Two hundred fifty-eight patients with LRDA-ba and 258 matched controls with GRDA were identified. Statistically significant findings included that patients with LRDA-ba were more likely to have presented with an ischemic stroke (LRDA-ba 12.4% vs. GRDA 3.9%) or subdural hemorrhage (8.9% vs. 4.3%); those with GRDA were more likely to have a metabolic encephalopathy (GRDA 10.5% vs. LRDA-ba 3.5%) or "altered mental state" without clear etiology (12.5% vs. 4.3%). Patients with LRDA-ba were significantly more likely to have a background EEG asymmetry (LRDA-ba 62.0% vs. GRDA 25.6%) or focal (arrhythmic) slowing (40.3% vs. 15.5%), and acute (65.5% vs. 46.1%) or focal (49.6% vs. 28.3%) abnormalities on computed tomography scan. Patients with LRDA-ba were more likely to have focal sporadic epileptiform discharges (95.4% vs. 37.9%), lateralized periodic discharges (32.2% vs. 5.0%), and focal electrographic seizures (33.3% vs. 11.2%); however, patients with LRDA-ba alone (i.e., without sporadic epileptiform discharges or PDs) showed only a trend toward increased seizures (17.3%) compared with a matched group of patients with GRDA alone (9.9%, P = 0.08). CONCLUSIONS: Patients with LRDA-ba had a higher proportion of acute focal abnormalities compared with a matched group of patients with GRDA. The LRDA-ba was associated with additional evidence of focal cortical excitability on EEG (sporadic epileptiform discharges and lateralized periodic discharges) and seizures but with only a trend toward increased seizures when other signs of focal excitability were absent.

Quantitative assessment of burst suppression as a predictor of seizure recurrence in refractory status epilepticus.

OBJECTIVE: To determine whether quantitative EEG analysis of burst suppression can predict seizure recurrence in patients with refractory status epilepticus (RSE) being treated with anesthetic doses of continuous IV antiseizure medications (cIVASM). METHODS: Quantitative assessment of burst suppression (including epileptiform discharges [EDs] and evolution) in 31 occasions (from 27 patients), and correlation with seizure recurrence up to 48 hours post sedative wean. RESULTS: Occasions resulting in seizure recurrence (vs. no seizure recurrence) had lower burst (8.4 vs. 10.6 µV) and interburst interval (IBI) (4.2 vs. 4.8 µV) average amplitude, duration (bursts 2.8 vs. 3.6 s: IBIs 3.6 vs. 4.4 s); and burst total power (0.4 vs. 0.7 µV2). Bursts (0.86 vs. 0.60) and IBIs (0.28 vs. 0.07) with EDs, higher number of EDs within bursts (mean 2.1 vs. 1.4) and IBIs (0.6 vs. 0.2), and positive evolution measures all predicted seizure recurrence, although EDs had the greatest adjusted odds ratio on multivariate analysis. CONCLUSIONS: For patients in burst suppression, successful wean of cIVASM was not determined by classical burst suppression measures, but instead how "epileptiform" bursts and IBIs were, as determined by EDs in both bursts and IBIs and surrogates for evolution within bursts. SIGNIFICANCE: If confirmed, these objective measures could be used during clinical care to help determine when to wean cIVASM in patients with RSE.

Association of Serum Pyridoxal Phosphate Levels with Established Status Epilepticus.

BACKGROUND: The objective of this study was to determine the prevalence of pyridoxine deficiency, measured by pyridoxal phosphate (PLP) levels, in patients admitted to the hospital with established (benzodiazepine-resistant) status epilepticus (SE) (eSE) and to compare to three control groups: intensive care unit (ICU) patients without SE (ICU-noSE), non-ICU inpatients without SE (non-ICU), and outpatients with or without a history of epilepsy (outpatient). METHODS: This retrospective cohort study was conducted at the University of North Carolina Hospitals and Yale New Haven Hospital. Participants included inpatients and outpatients who had serum PLP levels measured during clinical care between January 2018 and March 2021. The first PLP level obtained was categorized as normal (> 30 nmol/L), marginal (≤ 30 nmol/L), deficient (≤ 20 nmol/L), and severely deficient (≤ 5 nmol/L). RESULTS: A total of 293 patients were included (52 eSE, 40 ICU-noSE, 44 non-ICU, and 157 outpatient). The median age was 55 (range 19-99) years. The median PLP level of the eSE group (12 nmol/L) was lower than that of the ICU-noSE (22 nmol/L, p = 0.003), non-ICU (16 nmol/L, p = 0.05), and outpatient groups (36 nmol/L, p < 0.001). Patients with eSE had a significantly higher prevalence of marginal and deficient PLP levels (90 and 80%, respectively) than patients in each of the other three groups (ICU-noSE: 70, 50%; non-ICU: 63, 54%; outpatient: 38, 21%). This significantly higher prevalence persisted after correcting for critical illness severity and timing of PLP level collection. CONCLUSIONS: Our study confirms previous findings indicating a high prevalence of pyridoxine deficiency (as measured by serum PLP levels) in patients with eSE, including when using a more restricted definition of pyridoxine deficiency. Prevalence is higher in patients with eSE than in patients in all three control groups (ICU-noSE, non-ICU, and outpatient). Considering the role of pyridoxine, thus PLP, in the synthesis of γ-aminobutyric acid and its easy and safe administration, prospective studies on pyridoxine supplementation in patients with eSE are needed.

Pregabalin for Recurrent Seizures in Critical Illness: A Promising Adjunctive Therapy, Especially for cyclic Seizures.

BACKGROUND: Pregabalin (PGB) is an effective adjunctive treatment for focal epilepsy and acts by binding to the alpha2-delta subunit of voltage-gated calcium channels to reduce excitatory neurotransmitter release. Limited data exist on its use in the neurocritical care setting, including cyclic seizures-a pattern of recurrent seizures occurring at nearly regular intervals. Although the mechanism underpinning cyclic seizures remains elusive, spreading excitation linked to spreading depolarizations may play a role in seizure recurrence and periodicity. PGB has been shown to increase spreading depolarization threshold; hence, we hypothesized that the magnitude of antiseizure effect from PGB is more pronounced in patients with cyclic versus noncyclic seizures in a critically ill cohort with recurrent seizures. METHODS: We conducted a retrospective case series of adults admitted to two academic neurointensive care units between January 2017 and March 2019 who received PGB for treatment of seizures. Data collected included demographics, etiology of brain injury, antiseizure medications, and outcome. Continuous electroencephalogram recordings 48 hours before and after PGB administration were reviewed by electroencephalographers blinded to the administration of antiseizure medications to obtain granular data on electrographic seizure burden. Cyclic seizures were determined quantitatively (i.e., < 50% variation of interseizure intervals for at least 50% of consecutive seizures). Coprimary outcomes were decrease in hourly seizure burden in minutes and decrease in seizure frequency in the 48 hours after PGB initiation. We used nonparametric tests for comparison of seizure frequency and burden and segmented linear regression to assess PGB effect. RESULTS: We included 16 patients; the median age was 69 years, 11 (68.7%) were women, three (18.8%) had undergone a neurosurgical procedure, and five (31%) had underlying epilepsy. All seizures had focal onset; ten patients (62.5%) had cyclic seizures. The median hourly seizure burden over the 48 hours prior to PGB initiation was 1.87 min/hour (interquartile range 1.49-8.53), and the median seizure frequency was 1.96 seizures/hour (interquartile range 1.06-3.41). In the 48 hours following PGB (median daily dose 300 mg, range 75-300 mg), the median number of seizures per hour was reduced by 0.80 seizures/hour (95% confidence interval 0.19-1.40), whereas the median hourly seizure burden decreased by 1.71 min/hour (95% confidence interval 0.38-3.04). When we compared patients with cyclic versus noncyclic seizures, there was a relative decrease in hourly seizure frequency (- 86.7% versus - 2%, p = 0.04) and hourly seizure burden (- 89% versus - 7.8%, p = 0.03) at 48 hours. CONCLUSIONS: PGB was associated with a relative reduction in seizure burden in neurocritically ill patients with recurrent seizures, especially those with cyclic seizures, and may be considered in the therapeutic arsenal for refractory seizures. Whether this effect is mediated via modulation of spreading depolarization requires further study.

Essential oil related seizures (EORS): A multi-center prospective study on essential oils and seizures in adults.

OBJECTIVE: Essential oils (EOs) like eucalyptus and camphor have pro-convulsant properties. These EOs are present in many over- the- counter balms and oils. The effect of exposure to these EOs and occurrence of seizure is not systematically studied. The aim of this study was to evaluate the relationship between essential oils and the first episode of seizure and breakthrough seizures in known epileptic patients. METHODS: This was a multi-center prospective study, conducted in four hospitals over four years. Every person presenting with the first episode of seizure or breakthrough seizure was asked about exposure to EOs, mode of exposure, time to onset of a seizure in relationship to exposure, duration of seizure, type of seizure, and antiepileptic drug therapy. RESULTS: During the four-year period there were 55 patients with essential oil-related seizure (EORS). 22(40 %) had essential oil-induced seizures (EOIS) and 33(60 %) had essential oil-provoked seizures (EOPS). The female: male ratio was 1:1.1, the age of the patients ranged from 8 months to 77 years. In the EOIS group, 95 % had generalized tonic-clonic seizures and 5% had focal impaired awareness seizures. In the EOPS group, 42.4 % had focal impaired awareness seizures, 27.3 % generalized tonic-clonic seizures, 15 % focal to bilateral tonic-clonic seizures, and 15 % focal aware motor seizures. EOs implicated were preparations containing eucalyptus and camphor. CONCLUSION: Exposure to essential oils of eucalyptus and camphor is an under-recognized cause of the first and breakthrough seizure. Identifying the true causative factor will prevent unnecessary antiepileptic drug therapy and future recurrence.

Essential oil-related status epilepticus: A small case series study.

OBJECTIVE: Essential oils are plant-derived oils and are widely used as an over-the-counter remedy for common ailments. Many essential oils are found to have proconvulsant effects. Here we report a small case series of 3 adults with eseential oil-related status epilepticus. METHODS: This was an observational study conducted in a tertiary care hospital in south India from January 2018 to December 2019. We collected the demographic, clinical, and imaging features of all cases of status epilepticus resulting from exposure to essential oils. Cases of status epilepticus secondary to all other causes were excluded. RESULTS: There were 3 young adults with essential oil-related status epilepticus. Two had de novo generalized tonic-clonic status epilepticus, and 1 with posttraumatic occipital lobe epilepsy had focal-impaired awareness status epilepticus. The first 2 cases presented with histories of ingestion of eucalyptus oil. The third case had focal-impaired awareness status epilepticus after topical application of various balms containing eucalyptus and camphor. CONCLUSIONS: Proconvulsant essential oils of eucalyptus and camphor can cause both generalized and focal status epilepticus. Physicians dealing with patients of status epilepticus should enquire about the exposure to proconvulsant essential oils.

Eucalyptus oil inhalation-induced seizure: A novel, underrecognized, preventable cause of acute symptomatic seizure.

Eucalyptus oil (EO) is an essential oil that is widely used across the globe as an over-the-counter remedy for common ailments. EO-induced seizure (EOIS) has not been recognized as an entity, and physicians rarely ask the history of exposure to eucalyptus oil when seeing a patient with first episode of seizure. Here we report 10 cases of EO inhalation-induced seizures seen over the past 2 years in three tertiary care hospitals. Eight patients had GTCS and two had CPS. We aim to raise awareness of seizures induced by exposure to eucalyptus oil.

Over-the-counter self-medication leading to intracranial hypertension in a young lady.

Intracranial hypertension (idiopathic-IIH and secondary) is a potentially treatable condition. Although various factors such as female gender and obesity, certain drugs have been implicated as risk factors for IIH, there remains a lack of clarity in the exact causal-effect relationship. In India, self-medication by obtaining drugs over the counter due to lack of adequate drug regulation and ignorance of the public is a very common practice with a potential for severe adverse effects. We present a case of a young lady who has developed intracranial hypertension possibly due to self-medication with steroids and cyproheptadine, obtained over the counter.

Clinical, electrophysiological, imaging, and ultrastructural description in 68 patients with neuronal ceroid lipofuscinoses and its subtypes.

PURPOSE: We evaluated the clinical, electrophysiological, imaging, and ultrastructural features of neuronal ceroid lipofuscinoses and its subtypes. METHODS: The clinical, electrophysiological, imaging, histopathological, and ultrastructural features of 68 (age at onset: 4.3 ± 5.4 years) neuronal ceroid lipofuscinoses and its subtypes (infantile neuronal ceroid lipofuscinoses [9], late infantile neuronal ceroid lipofuscinoses [34], juvenile neuronal ceroid lipofuscinoses [23], and adult neuronal ceroid lipofuscinoses [2] were evaluated. Skin (n = 56), brain (n = 12), muscle (n = 4) and nerve (n = 1) biopsies confirmed the diagnosis. RESULTS: Clinical manifestations were milestone regression (93%), involuntary movements (92%), seizures (89%), myoclonus (79%), and visual impairment (68%). Response to anticonvulsants was unsatisfactory. Electroencephalography (n = 59) was abnormal in 90%: background slowing (90%); epileptiform discharges (71%), and photoparoxysmal response (4/21). Visual-evoked (n = 33) and somatosensory evoked (n = 40) potentials were abnormal in 62% and 63% of patients. Cranial computed tomography (n = 33) showed diffuse cerebral (61%) and cerebellar (27%) atrophy. Magnetic resonance imaging was abnormal in all 43 patients who were scanned: diffuse atrophy (100%), cerebellar atrophy (40%), leukoencephalopathy (65%), and thalamic T2 W hypointensity (33%). Dermal inclusions such as curvilinear inclusions were the most common abnormality: late infantile neuronal ceroid lipofuscinoses (97%), juvenile neuronal ceroid lipofuscinoses (100%), and infantile neuronal ceroid lipofuscinoses (88%). Additional fingerprint inclusions were noted: juvenile neuronal ceroid lipofuscinoses (43%), late infantile neuronal ceroid lipofuscinoses (15%), and infantile neuronal ceroid lipofuscinoses (13%). Granular osmiophilic deposits were noted in 50% of infantile neuronal ceroid lipofuscinoses. In 75% of patients, there was good correlation between the clinical subtype and ultrastructural inclusion pattern. In 27% of neuronal ceroid lipofuscinoses, multiple inclusions were noted. CONCLUSIONS: The diagnosis of neuronal ceroid lipofuscinoses should be considered in individuals with characteristic clinical presentations and characteristic ultrastructural dermal inclusions. Three fourths showed morphological correlation of the inclusions with neuronal ceroid lipofuscinoses subtype.

Diffusion tensor imaging (DTI) and its clinical correlates in drug naïve Wilson's disease.

The purpose is to evaluate white matter (WM) abnormalities in Wilson's disease (WD) using the technique of diffusion tensor imaging (DTI). The prospective case-control study comprised of 15 drug-naïve patients with WD and 15 controls. The phenotype of subjects was evaluated. The DTI/conventional MRI was acquired (3T MRI): Fractional anisotropy (FA) and mean diffusivity (MD) values were extracted from regions of interest placed in pons, midbrain, bilateral frontal and occipital cerebral white matter, bilateral internal capsules (IC), middle cerebellar peduncles (MCP) and corpus callosum (CC). Six patients showed lobar WM signal changes on T(2)-Weighted (T2W)/Fluid attenuation inversion recovery (FLAIR) images while remaining had normal appearing WM. MD was significantly increased in the lobar WM, bilateral IC and midbrain of WD patients. FA was decreased in the frontal and occipital WM, bilateral IC, midbrain and pons. Normal-appearing white matter on FLAIR images showed significantly increased MD and decreased FA values in both frontal and occipital lobar WM and IC compared with those in controls. Correlation of clinical scores and DTI metrics revealed positive correlation between neurological symptom score (NSS) and MD of anterior limb of right internal capsule, Chu stage and MD of frontal and occipital WM. Negative correlation was observed between the Modified Schwab and England Activities of Daily Living (MSEADL) score and MD of bilateral frontal and occipital WM and IC. This is the probably the first study to reveal widespread alterations in WM by DTI metrics in drug naïve WD. DTI analysis revealed lobar WM abnormalities which is less frequently noted on conventional MRI and suggests widespread WM abnormalities in WD. It may be valuable in assessing the true extent of involvement and therefore the severity of the illness.