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Introduction Stiff-person syndrome (SPS), first described in 1956 by Moersch and Woltman, is a progressive autoimmune disorder with core features of chronic fluctuating progressive truncal and limb rigidity and painful muscle spasms leading to gait difficulties, falls and an appearance that resembles tin soldiers. The syndrome is a rare, highly disabling disorder of the central nervous and frequently results in significant disability. Understanding of the etiology, clinical spectrum, diagnostic workup and therapeutic modalities for this painful and disabling disorder has vastly evolved over the past few years with more confidence in classifying and treating the patients. The purpose of this review is to increase the awareness, early detection, and treatment of this disabling disease. Method PubMed was searched, all date inclusive, using the following phrases: stiff person syndrome,anti-Glutamic acid decarboxylase (Anti-GAD) antibody syndrome, Progressive encephalomyelitis with rigidity and myoclonus (PERM), and Paraneoplastic Stiff Person syndrome. No filters or restrictions were used. A total of 888 articles were identified. Results The results were narrowed to 190 citations after excluding non-English and duplicate reports. Clinical presentation, laboratory testing, treatment, and prognosis were categorized and summarized. Discussion In this article we will discuss the epidemiology, presentation and classification. Explain the pathophysiology of SPS and the autoimmune mechanisms involved. Discuss the diagnostic approach and treatments available, as well as, the prognosis and outcome.

We reviewed the electronic medical records (EMR) of patients hospitalized during the peak of the pandemic, March 1st through March 31st, to document the type and frequency of neurological problems seen in patients with COVID-19 at presentation to the emergency room. Secondary aims were to determine: 1) the frequency of neurological complaints during the hospital stay; 2) whether the presence of any neurological complaint at presentation or any of the individual types of neurological complaints at admission predicted three separate outcomes: death, length of hospital stay, or the need for intubation; and 3) if the presence of any neurological complaint or any of the individual types of neurological complaints developed during hospital stay predicted the previous three outcomes. Setting The Louisiana Health Sciences Center – New Orleans Institutional Review Board and the University Medical Center Clinical Research Review Committee approved the study protocol. Data acquisition We reviewed the electronic medical records (EMR) of patients hospitalized during March (March 1st through March 31st) 2020 at the University Medical Center New Orleans (UMCNO), who tested positive for SARS-CoV-2 during the same hospitalization. The EMR team generated a list of 257 patients admitted for COVID-19. We excluded seven patients because of a negative COVID-19 test result or incomplete medical record documentation. Three neurology residents (DC, MS, DB) reviewed the EMR in detail to capture the relevant medical history, clinical course, and laboratory test results and abstracted data into an electronic data collection spreadsheet. We recorded the presentation or development of the following neurological complaints: headache, syncope, altered mental status, seizure, status epilepticus, and ischemic or hemorrhagic stroke. Statistical analysis We used "R" (statistics software) and Microsoft Excel to generate summary tables. To analyse hospital length of stay or death, we fitted a competing risks proportional hazards model for time to discharge or death using the crr() function in R version 4.0.0. The competing risks model allowed the analysis of hospital stay, taking into account that the censoring of cases due to death was not random. To predict the likelihood of intubation, we used the glm() function in R to fit a logistic regression model. For each model, we determined baseline demographic variables predictive of the outcomes and generated adjusted models. For variables with less than five cases per cell, we reported the p-values for Fisher's Exact Test. The analyses and results are published in: Chachkhiani, David et al. " Neurological complications in a predominantly African American population of COVID-19 predict worse outcomes during hospitalization." Clinical Neurology and Neurosurgery (in press). These data will be useful for researchers trying to build larger datasets regarding COVID19 neurological complications for metanalysis or to answer other questions requiring larger sample sizes.

Whipple’s Disease (WD) was first described by George H. Whipple in 1907. Classic Whipple disease (CWD) is a systemic chronic infection by Tropheryma whipplei (T. whipplei) that can involve various organ systems such as gastrointestinal tract, joints, and central nervous system (CNS). Central nervous system Whipple’s disease (CNS- WD) can be a part of the classical WD, a recurrent phenomenon or an isolated disease. It encompasses a wide array of clinical manifestations depending on the anatomic region affected by the pathological process. Diagnosis is made by polymerase chain reaction testing. It is vital to implement an aggressive mode of treatment to reduce the chances of complications like cognitive impairment, or disease recurrence, even many years later.

Highlights • The most common neurological chief complaint in patients with COVID-19 is Altered Mental Status. • A neurological chief complaint at admission is associated with prolonged hospital stays, death, and intubation. • Altered Mental Status at admission is associated with significantly prolonged hospital stay. • Patients with Altered Mental Status during the hospital stay, as well as those who had seizures, were more likely to require intubation., People with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, COVID-19, can have neurological problems including headache, anosmia, dysgeusia, altered mental status (AMS), ischemic stroke with or without large vessel occlusion, and Guillen-Barre Syndrome. Louisiana was one of the states hit hardest by the pandemic with just over 57,000 laboratory-confirmed cases of COVID-19 by the end of June 2020. We reviewed the electronic medical records (EMR) of patients hospitalized during the peak of the pandemic, March 1st through March 31st, to document the type and frequency of neurological problems seen in patients with COVID-19 at presentation to the emergency room. Secondary aims were to determine: 1) the frequency of neurological complaints during the hospital stay; 2) whether the presence of any neurological complaint at presentation or any of the individual types of neurological complaints at admission predicted three separate outcomes: death, length of hospital stay, or the need for intubation; and 3) if the presence of any neurological complaint or any of the individual types of neurological complaints developed during hospital stay predicted the previous three outcomes. A large proportion of our sample (80 %) was African American and had hypertension (79 %). Out of 250 patients, 56 (22 %) patients died, and 72 (29 %) patients required intubation. Thirty-four (14 %) had a neurological chief complaint at presentation; the most common neurological chief complaints in the entire sample were altered mental status (AMS) (8 %), headache (2 %), and syncope (2 %). We used a competing risk model to determine whether neurological symptoms at presentation or during hospital stay were predictors of prolonged hospital stay and death. To establish whether neurological symptoms were associated with higher odds of intubation, we used logistic regression. Age was the only significant demographic predictor of death and hospital stay. The HR (95 %CI) for remaining in the hospital for a ten-year increase in age was 1.2, (1.1, 1.3, p

Here, in Part II of a duology on the characterization and potential treatment for COVID-19, we characterize the application of an innovative treatment regimen for the prevention of the transition from mild to severe COVID-19, as well as detail an intensive immunotherapy intervention hypothesis. We propose as a putative randomized controlled trial that high-dose methotrexate with leucovorin (HDMTX-LR) rescue can abolish ‘PANIC’, thereby ‘left-shifting’ severe COVID-19 patients to the group majority of those infected with the SARS-CoV-2 virus, who are designated as having mild, even asymptomatic, disease. HDMTX-LR is endowed with broadly pleiotropic properties and is a repurposed, generic, inexpensive, and widely available agent which can be administered early in the course of severe COVID-19 thus rescuing the critical and irreplaceable gas-exchange alveoli. Further, we describe a preventative treatment intervention regimen for those designated as having mild to moderate COVID-19 disease, but who exhibit features which herald the transition to the severe variant of this novel Coronavirus. Both of our proposed hypothesis-driven questions should be urgently subjected to rigorous assessment in the context of randomized controlled trials, in order to confirm or refute the contention that the approaches characterized herein, are in fact capable of exerting mitigating, if not abolishing, effects upon the SARS-CoV-2 triggering of the ‘PANIC Attack’. Confirmation of our immunotherapy hypothesis would have far-reaching ramifications for the current pandemic, along with yielding invaluable lessons from which we can more effectively prepare for the next challenge to global health.

The coronavirus disease 2019 (COVID-19) pandemic has produced a world-wide collapse of social and economic infrastructure, as well as constrained our freedom of movement. This respiratory tract infection is nefarious in how it targets the most distal and highly vulnerable aspect of the human bronchopulmonary tree, specifically, the delicate yet irreplaceable alveoli that are responsible for the loading of oxygen upon red cell hemoglobin for use by all of the body's tissues. In most symptomatic individuals, the disease is a mild immune-mediated syndrome, with limited damage to the lung tissues. About 20% of those affected experience a disease course characterized by a cataclysmic set of immune activation responses that can culminate in the diffuse and irreversible obliteration of the distal alveoli, leading to a virtual collapse of the gas-exchange apparatus. Here, in Part I of a duology on the characterization and potential treatment for COVID-19, we define severe COVID-19 as a consequence of the ability of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to trigger what we now designate for the first time as a 'Prolific Activation of a Network-Immune-Inflammatory Crisis', or 'PANIC' Attack, in the alveolar tree. In Part II we describe an immunotherapeutic hypothesis worthy of the organization of a randomized clinical trial in order to ascertain whether a repurposed, generic, inexpensive, and widely available agent is capable of abolishing 'PANIC'; thereby preventing or mitigating severe COVID-19, with monumental ramifications for world health, and the global pandemic that continues to threaten it.

Introduction Altered Mental Status (AMS) is a common neurological complication in patients hospitalized with the diagnosis of COVID-19 (Umapathi et al., 2020; Liotta et al., 2020). Studies show that AMS is associated with death and prolonged hospital stay. In addition to respiratory insufficiency, COVID-19 causes multi-organ failure and multiple metabolic derangements, which can cause AMS, and the multi-system involvement could account for the prolonged hospital stay and increased mortality. In this study, we built on our previous publication (Chachkhiani et al., 2020) using a new, larger cohort to investigate whether we could reproduce our previous findings while addressing some of the prior study’s limitations. Most notably, we sought to determine whether AMS still predicted prolonged hospital stay and increased mortality after controlling for systemic complications such as sepsis, liver failure, kidney failure, and electrolyte abnormalities. Objectives The primary purpose was to document the frequency of AMS in patients with COVID-19 at the time of presentation to the emergency room. Secondary aims were to determine: 1) if AMS at presentation was associated with worse outcomes as measured by prolonged hospitalization and death; and 2) if AMS remained a predictor of worse outcome after adjusting for concomitant organ failure and metabolic derangements. Results Out of 367 patients, 95 (26%) had AMS as a main or one of the presenting symptoms. Our sample has a higher representation of African Americans (53%) than the US average and a high frequency of comorbidities, such as obesity (average BMI 29.1), hypertension (53%), and diabetes (30%). Similar to our previous report, AMS was the most frequent neurological chief complaint. At their admission, out of 95 patients with AMS, 83 (88%) had organ failure or one of the systemic problems that could have caused AMS. However, a similar proportion (86%) of patients without AMS had one or more of these same problems. Age, race, and ethnicity were the main demographic predictors. African Americans had shorter hospital stay [HR1.3(1.0,1.7),p = 0.02] than Caucasians. Hispanics also had shorter hospital stay than non-Hispanics [HR1.6(1.2,2.1), p = 0.001]. Hypoxia, liver failure, hypernatremia, and kidney failure were also predictors of prolonged hospital stay. In the multivariate model, hypoxia, liver failure, and acute kidney injury were the remaining predictors of longer hospital stay, as well as people with AMS at baseline [HR0.7(0.6,0.9), p

Background/Aims: To assess (1) the duration and symptoms present in participants with mild cognitive impairment (MCI) and (2) the impact of these variables on predicting conversion to Alzheimer’s disease (AD). Methods: Participants with MCI (n = 148) were assessed and followed systematically. Results: Decline in memory was reported as the first symptom in 118 of the cases. Converters had more symptoms (e.g. language decline, depression), and the combination of decline in memory and in performance of high-order social/cognitive activities as well as disorientation more often than nonconverters (p = 0.036). In an age-stratified Cox model, predictors of conversion to AD were shorter time since onset of memory decline and lower baseline MMSE score. Conclusions: Recent onset of memory decline with older age, decreased MMSE score, change in performance and disorientation indicate a greater likelihood of short-term conversion to AD.

Clinical assessment of domestic violence has traditionally relied on self-report methods of data collection, using structured interviews and lengthy questionnaires such as the MMPI-2. However, in certain situations such as court-ordered domestic violence evaluations, information obtained through self-report methods may be tainted because of willful impression management on the part of the client. The purpose of the current study was to compare self-report response styles of individuals with varying levels of domestic violence potential in order to determine whether the measures used could accurately differentiate between the groups. Individuals who were currently involved in child custody cases were court ordered to an anger assessment clinic to determine their potential for domestic violence because they had been accused of domestic abuse. Participants were classified into three groups: (a) documented domestic violence (n = 12), (b) high risk for domestic violence (n = 16), and (c) minimal risk for domestic violence (n = 24), and completed several measures of personality including the MMPI-2. Results indicated that the majority of individuals from all three groups used impression management techniques in an attempt to enhance their appearance. However, documented perpetrators of domestic violence still tended to score higher on specific measures of aggression despite their attempts to minimize. These results imply that individuals accused of domestic violence may employ impression management regardless of their guilt or innocence; therefore, the evaluation process should not disproportionately rely on self-reports.

Research on aggression and violence has consistently recognized two subtypes of aggressive behavior: a reactive or impulsive type and a predatory or premeditated type. Several studies have also demonstrated the importance of classifying aggressive behavior in relation to treatment/intervention outcome, suggesting that the extent to which neurobiological variables influence impulsive and premeditated aggressive behavior differs. Despite these results, few neurobiological studies of aggression have attempted to classify violent behavior according to these subtypes. This article selectively reviews literature on the neurobiological correlates of aggression focusing on studies that have specifically examined or compared aggressive subtypes (impulsive or premeditated). In addition, a clinically effective classification scheme for aggressive behavior is presented along with supporting personality and psychophysiological data. Issues relevant to the study, identification, and treatment of aggressive beh...

The present study employed a battery of verbal tests that included a broad range of executive demands to demonstrate the differential contributions of language and executive function to the performance decrement observed in individuals who display impulsive aggressive (IA) outbursts. A profile analysis revealed that despite not differing on tasks requiring limited verbal output, the IAs deviated further from nonaggressive controls as the tasks required increasing spontaneous organization. Results suggest that language ability per se is not impaired in IAs; rather inefficient executive functioning is responsible for their significantly poorer performance on complex verbal tasks.

Aggressive behavior has traditionally been classified into two distinct subtypes: an affective, impulsive aggressive display or a planned, predatory aggressive act. While a number of investigations have examined the clinical and physiological correlates in impulsive aggressive individuals, very little research has been conducted on those individuals engaging in predominantly premeditated aggressive acts. The present study compared a group of premeditated aggressive psychiatric outpatients with a group of normal, non-aggressive control subjects on personality, neuropsychological and cognitive psychophysiological measures. Consistent with previous work, premeditated aggressors did not differ significantly from controls on most measures of neuropsychological and psychophysiological function. Premeditated aggressors did show significant personality pathology scoring higher on measures of impulsivity, verbal and physical aggression, anger, hostility, psychoticism and neuroticism. Overall, these results suggest a distinctive personality style that is associated with aggressive behavior. With respect to this and previous work, it is suggested that the physiological aspects of behavioral control play a key role in the type of aggressive behavior displayed.

Burst suppression (BS) consists of bursts of high-voltage slow and sharp wave activity alternating with periods of background suppression in the electroencephalogram (EEG). When induced by deep anesthesia or encephalopathy, BS is bihemispheric and is often viewed as a non-epileptic phenomenon. In contrast, unihemispheric BS is rare and its clinical significance is poorly understood. We describe here two cases of unihemispheric BS. The first patient is a 56-year-old woman with a left temporoparietal tumor who presented in convulsive status epilepticus. EEG showed left hemispheric BS after clinical seizure termination with lorazepam and propofol. The second patient is a 39-year-old woman with multiple medical problems and a vague history of seizures. After abdominal surgery, she experienced a convulsive seizure prompting treatment with propofol. Her EEG also showed left hemispheric BS. In both cases, increasing the propofol infusion rate resulted in disappearance of unihemispheric BS and clinical improvement. The prevailing view that typical bihemispheric BS is non-epileptic should not be extrapolated automatically to unihemispheric BS. The fact that unihemispheric BS was associated with clinical seizure and resolved with propofol suggests that, in both cases, an epileptic mechanism was responsible for unihemispheric BS.

Intractable epilepsy with painful partial motor seizures is a relatively rare and difficult disorder to treat. We evaluated the usefulness of botulinum toxin to reduce ictal pain. Two patients received two or four botulinum toxin (BTX) injections at one-to-two-month intervals. Patient 1 had painful seizures of the right arm and hand. Patient 2 had painful seizures involving the left foot and leg. Injections were discontinued after improved seizure control following resective surgery. Both patients received significant pain relief from the injections with analgesia lasting at least two months. Seizure severity was reduced, but seizure frequency and duration were unaffected. For these patients, BTX was effective in temporarily relieving pain associated with muscle contraction in simple partial motor seizures. Our findings do not support the hypothesis that modulation of motor end-organ feedback affects focal seizure generation. BTX is a safe and reversible treatment that should be considered as part of adjunctive therapy after failure to achieve control of painful partial motor seizures.

This study compared the behavioral effects of 3 anticonvulsants in impulsive aggressive men. In a double-blind, placebo-controlled, parallel groups design, participants were randomly assigned to 1 of 4 6-week treatments: phenytoin (n = 7), carbamazepine (n = 7), valproate (n = 7), or placebo (n = 8). The efficacy measure was the average aggression score, a global severity index from the Overt Aggression Scale (J. M. Silver & S. C. Yudofsky, 1991). Analysis showed a significant reduction in impulsive aggression during all 3 anticonvulsant conditions compared with placebo. However, the treatment effect during carbamazepine administration was slightly delayed compared with phenytoin and valproate. These findings suggest that increased use of anticonvulsants could make a significant impact in the control of impulsive aggression in both mental health and criminal justice settings.

Although obsessive—compulsive personality disorder (OCPD) is an Axis II diagnosis that is not commonly associated with behavioral disinhibition, the literature contains reports of occasional explosive aggressive outbursts. Existing explanations of OCPD etiology do not address the coexistence of compulsive and impulsive features witnessed in some subpopulations of patients. In this study, the authors present a compensatory theory of OCPD in an effort to explain clinical observations of an unexpectedly large number of OCPD diagnoses among patients clinic referred and self-referred for aggression problems.

In the research literature, aggressive behavior has traditionally been classified into two distinct subtypes, impulsive or premeditated. Impulsive aggression is defined as a hair-trigger aggressive response to provocation with loss of behavioral control. Premeditated aggression is defined as a planned or conscious aggressive act, not spontaneous or related to an agitated state. The present study outlines the development of a clinically useful self-report instrument, the Impulsive/Premeditated Aggression Scales (IPAS), designed to characterize aggressive behavior as predominately impulsive or predominately premeditated in nature. The IPAS showed strong reliability and validity. Analysis of the IPAS scores demonstrated the presence of two types of aggressive behavior, impulsive and premeditated, in men referred for anger problems. The aggression of most individuals in the present sample was characterized as predominately impulsive in nature (90%).

Ž. The present study examines the behavioral and psychophysiological effects of phenytoin PHT in individuals who display impulsive-aggressive outbursts. In a double-blind placebo-controlled crossover design, individuals meeting previously established criteria for impulsive aggression were administered PHT and placebo during separate 6-week Ž. conditions. The efficacy measures used were the Overt Aggression Scale OAS and the Profile of Mood States Ž. Ž . POMS . Psychophysiological measures evoked potentials were taken at baseline and at the end of each 6-week condition. Photic stimulation was used to evoke the mid-latency P1N1P2 waveform complex. Analysis indicated a significant decrease in the frequency of impulsive-aggressive outbursts during PHT administration compared to baseline and placebo. Analysis of the psychophysiological data showed significantly increased P1 amplitude and significantly longer N1 latency during PHT administration. In addition, a reduction in N1 amplitude during PHT administration was also suggested. These findings indicate reparation of physiological abnormalities previously observed in impulsive-aggressive individuals and imply more efficient sensory processing and effective orienting of attention. Taken together, these results provide insight as to the physiological mechanisms by which PHT serves to ameliorate impulsive-aggressive behavior. 2001 Elsevier Science Ireland Ltd. All rights reserved.

The clinical diagnosis of Creutzfeldt-Jakob disease (CJD) is largely based on the 1998 World Health Organization diagnostic criteria. Unfortunately, rigid compliance with these criteria may result in failure to recognize sporadic CJD (sCJD), especially early in its course when focal findings predominate and traditional red flags are not yet present. A 61-year-old man presented with a 3-week history of epilepsia partialis continua (jerking of the left upper extremity) and a 2-week history of forgetfulness and left hemiparesis; left hemisensory neglect was also detected on admission. Repeated brain magnetic resonance imaging (MRI) showed areas of restricted diffusion in the cerebral cortex, initially on the right but later spreading to the left. Electroencephalography (EEG) on hospital days 7, 10, and 14 showed right-sided periodic lateralized epileptiform discharges. On day 20, the EEG showed periodic sharp wave complexes leading to a diagnosis of probable sCJD and subsequently to definite sCJD with brain biopsy. Neurological decline was relatively fast with generalized myoclonus and akinetic mutism developing within 7 weeks from the onset of illness. CJD was not immediately recognized because of the patient’s focal/lateralized manifestations. Focal/lateralized clinical, EEG, and MRI findings are not uncommon in sCJD and EEG/MRI results may not be diagnostic in the early stages of sCJD. Familiarity with these caveats and with the most current criteria for diagnosing probable sCJD (University of California San Francisco 2007, MRI-CJD Consortium 2009) will enhance the ability to recognize sCJD and implement early safety measures.

Introduction Typical spike-and-wave activity (TSWA) in the electroencephalogram (EEG) indicates idiopathic generalized epilepsy (IGE). IGE-related nonconvulsive status epilepticus (NCSE) is typically an absence status epilepticus (ASE). ASE and TSWA respond dramatically to benzodiazepines. Patients with no history of seizure/epilepsy may develop ASE “de novo” in the context of an acute brain disorder. However, we are aware of only one previous case of de novo ASE with TSWA in hypoxic-ischemic brain injury. Case Presentation A 65-year-old man, with congestive heart failure and history of substance abuse, survived cardiorespiratory arrest after 18 minutes of cardiopulmonary resuscitation. Post-resuscitation, the patient was in coma with intact brainstem function. Toxicology was positive for cocaine and marijuana. Eyelid myoclonus suggested NCSE, which was initially treated with lorazepam and fosphenytoin. EEG monitoring showed sustained TSWA confirming NCSE and demonstrating de novo ASE (the patient and his family never had seizure/epilepsy). The TSWA was resistant to lorazepam, levetiracetam, and low-dose midazolam; it was eliminated only with midazolam at a dose that resulted in burst-suppression (≥1.2 mg/kg/hour). Conclusion This is an unusual case of TSWA and hypoxic-ischemic brain injury in a patient with no history of seizure/epilepsy. The TSWA was relatively resistant to benzodiazepines suggesting that cerebral hypoxia-ischemia spared the thalamocortical apparatus generating TSWA but impaired the cortical/thalamic inhibitory circuits where benzodiazepines act to suppress TSWA. Albeit rare, ‘posthypoxic’ TSWA offers us some valuable insights for classifying and managing nonconvulsive status epilepticus.

The COVID-19 pandemic has devastated individuals, families, and institutions throughout the world. Despite the breakneck speed of vaccine development, the human population remains at risk of further devastation. The decision to not become vaccinated, the protracted rollout of available vaccine, vaccine failure, mutational forms of the SARS virus, which may exhibit mounting resistance to our molecular strike at only one form of the viral family, and the rapid ability of the virus(es) to hitch a ride on our global transportation systems, means that we are will likely continue to confront an invisible, yet devastating foe. The enemy targets one of our human physiology’s most important and vulnerable life-preserving body tissues, our broncho-alveolar gas exchange apparatus. Notwithstanding the fear and the fury of this microbe's potential to raise existential questions across the entire spectrum of human endeavor, the application of an early treatment intervention initiative may represent a crucial tool in our defensive strategy. This strategy is driven by evidence-based medical practice principles, those not likely to become antiquated, given the molecular diversity and mutational evolution of this very clever “world traveler”.