FDG-PET and MRI in the Evolution of New-Onset Refractory Status Epilepticus.

BACKGROUND AND PURPOSE: New-onset refractory status epilepticus is a clinical condition characterized by acute and prolonged pharmacoresistant seizures without a pre-existing relevant neurologic disorder, prior epilepsy, or clear structural, toxic, or metabolic cause. New-onset refractory status epilepticus is often associated with antineuronal antibodies and may respond to early immunosuppressive therapy, reflecting an inflammatory element of the condition. FDG-PET is a useful diagnostic tool in inflammatory and noninflammatory encephalitis. We report here FDG-PET findings in new-onset refractory status epilepticus and their correlation to disease activity, other imaging findings, and outcomes. MATERIALS AND METHODS: Twelve patients who met the criteria for new-onset refractory status epilepticus and who had FDG-PET and MR imaging scans and electroencephalography at a single academic medical center between 2008 and 2017 were retrospectively identified. Images were independently reviewed by 2 radiologists specialized in nuclear imaging. Clinical characteristics and outcome measures were collected through chart review. RESULTS: Twelve patients underwent 21 FDG-PET scans and 50 MR imaging scans. Nine (75%) patients were positive for autoantibodies. All patients had identifiable abnormalities on the initial FDG-PET in the form of hypermetabolism (83%) and/or hypometabolism (42%). Eight (67%) had medial temporal involvement. All patients (n = 3) with N-methyl-D-aspartic acid receptor antibodies had profound bilateral occipital hypometabolism. Initial MR imaging findings were normal in 6 (50%) patients. Most patients had some degree of persistent hyper- (73%) or hypometabolism (45%) after immunosuppressive therapy. FDG-PET hypometabolism was predictive of poor outcome (mRS 4-6) at hospital discharge (P = .028). CONCLUSIONS: Both FDG-PET hypometabolism and hypermetabolism are seen in the setting of new-onset refractory status epilepticus and may represent markers of disease activity.

Evidence-based guideline: intravenous immunoglobulin in the treatment of neuromuscular disorders: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.

OBJECTIVE: To assess the evidence for the efficacy of IV immunoglobulin (IVIg) to treat neuromuscular disorders. METHODS: The MEDLINE, Web of Science, and EMBASE databases were searched (1966-2009). Selected articles were rated according to the American Academy of Neurology's therapeutic classification of evidence scheme; recommendations were based on the evidence level. RESULTS AND RECOMMENDATIONS: IVIg is as efficacious as plasmapheresis and should be offered for treating Guillain-Barré syndrome (GBS) in adults (Level A). IVIg is effective and should be offered in the long-term treatment of chronic inflammatory demyelinating polyneuropathy (Level A). IVIg is probably effective and should be considered for treating moderate to severe myasthenia gravis and multifocal motor neuropathy (Level B). IVIg is possibly effective and may be considered for treating nonresponsive dermatomyositis in adults and Lambert-Eaton myasthenic syndrome (Level C). Evidence is insufficient to support or refute use of IVIg in the treatment of immunoglobulin M paraprotein-associated neuropathy, inclusion body myositis, polymyositis, diabetic radiculoplexoneuropathy, or Miller Fisher syndrome, or in the routine treatment of postpolio syndrome or in children with GBS (Level U). IVIg combined with plasmapheresis should not be considered for treating GBS (Level B). More data are needed regarding IVIg efficacy as compared with other treatments/treatment combinations. Most studies concluded IVIg-related serious adverse effects were rare. Given the variable nature of these diseases, individualized treatments depending on patient need and physician judgment are important.

Evidence-based guideline update: Plasmapheresis in neurologic disorders: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.

OBJECTIVE: To reassess the role of plasmapheresis in the treatment of neurologic disorders. METHODS: We evaluated the available evidence based on a structured literature review for relevant articles from 1995 through September 2009. In addition, due to revision of the definitions of classification of evidence since the publication of the previous American Academy of Neurology assessment in 1996, the evidence cited in that manuscript was reviewed and reclassified. RESULTS AND RECOMMENDATIONS: Plasmapheresis is established as effective and should be offered in severe acute inflammatory demyelinating polyneuropathy (AIDP)/Guillain-Barré syndrome (GBS) and in the short-term management of chronic inflammatory demyelinating polyneuropathy (Class I studies, Level A). Plasmapheresis is established as ineffective and should not be offered for chronic or secondary progressive multiple sclerosis (MS) (Class I studies, Level A). Plasmapheresis is probably effective and should be considered for mild AIDP/GBS, as second-line treatment of steroid-resistant exacerbations in relapsing forms of MS, and for neuropathy associated with immunoglobulin A or immunoglobulin G gammopathy, based on at least one Class I or 2 Class II studies (Level B). Plasmapheresis is probably not effective and should not be considered for neuropathy associated with immunoglobulin M gammopathy, based on one Class I study (Level B). Plasmapheresis is possibly effective and may be considered for acute fulminant demyelinating CNS disease (Level C). There is insufficient evidence to support or refute the use of plasmapheresis for myasthenia gravis, pediatric autoimmune neuropsychiatric disorders associated with streptococcus infection, and Sydenham chorea (Class III evidence, Level U).

The vibration quantitation scale (VQS): a simple, reproducible bedside measure of sensory function in multiple sclerosis.

OBJECTIVES: To assess the utility of a bedside measure of sensation (the Vibration Quantitation Scale (VQS)) in patients with multiple sclerosis (MS) and in normal controls. To correlate the VQS with the Kurtzke Expanded Disability Severity Score (EDSS) and sensory abnormalities in these patients. METHODS: We developed the VQS and tested its performance in patients with MS of various ages, MS types, and EDSS scores. We compared this with controls (normal volunteers or patients with other neurological diseases) who did not have sensory symptoms. In a subgroup, two examiners measured VQS independently at the same patient visit. A standard C-128 tuning fork was used for the VQS measurement. RESULTS: The VQS had a good inter-observer reproducibility (r=0.920, p<0.001). The VQS fell with increasing age in normals consistent with declining sensory function. The VQS was significantly lower in the multiple sclerosis patients compared with age - matched controls (p<0.001). Abnormalities in VQS were present in patients with brief duration of MS (<5 years) and low EDSS scores, correlating with the presence of sensory abnormalities early in the disease course in some patients. There was a strong correlation between the VQS and EDSS (r=-.509). The VQS correlated with abnormal sensation in the hands (r=0.310), but did not meet statistical significance for abnormal sensation in the feet or face. A second cohort of MS patients was studied using a modified VQS measure (single stimulation, omitting forehead measurement). This reconfirmed the correlation between the modified VQS and EDSS as well as with age. The modified VQS may be useful in clinical practice since it takes little time and is strongly correlated with the EDSS (r=0.578). CONCLUSIONS: The VQS provides a continuous sensory scale applicable in most patients with MS, which is measurable with standard bedside equipment, and which may avoid some of the pitfalls of sensory scoring in MS.

Sensory symptoms of multiple sclerosis: a hidden reservoir of morbidity.

OBJECTIVE: To assess the frequency and quality of sensory symptoms in a population of patients with Multiple Sclerosis (MS) and compare them with controls. DESIGN: Survey to target population and control group evaluating demographic data, data on disease course, presence of various symptoms of MS. SETTING: Neurological practices affiliated with a tertiary community hospital. PARTICIPANTS: 224 patients with MS, 93 controls of similar age and sex. RESULTS: Sensory symptoms were more common in MS patients than in controls, and differed in severity and quality. Fifty per cent described brief (seconds to hours) episodes of neurological dysfunction, significantly more often than in controls (P = 0.001). Pain was present at some time in similar percentages in patients and controls, but active pain problems were present more often in MS patients (P = 0.001). The qualitative description of pain in MS patients was more often neuropathic, with burning, itching, electric and formicatory pain, as opposed to throbbing, sharp or muscular pain. Pain was localized to arms, legs, trunk, hands, feet and face more often in the MS group. Lhermitte's phenomenon was present in two-thirds of patients at some time in their disease course. Twenty per cent of the patients identified themselves as having respiratory problems (Controls 7.5%, P = 0.005). Fatigue limited activity in 78% of patients, but only in 17% of controls (P = 0.001). Dizziness, memory dysfunction, and restless legs symptoms were all more frequent in patients. The self-rated 'worst' symptoms of MS was pain in 12%, fatigue in 17% and dizziness in 5%, a total of 34% of 'worst' symptoms. Sensory symptoms were present in patients with early disease and without disability as often as in disabled patients and in those with longer disease duration. There was however a strong correlation between the total number of sensory symptoms reported and the presence of disability in the MS patients. CONCLUSIONS: Sensory symptoms are common in MS patients. Pain syndromes, transient neurologic events, Lhermitte's phenomenon, fatigue, respiratory symptoms and vertigo were present significantly more frequently in patients with MS than in a control population and contributed to subjective morbidity. Future clinical trials assessing therapy in MS might include sensory symptoms as secondary endpoints to capture this 'hidden reservoir' of disease morbidity.

A reversible cause of hypercapnic respiratory failure: lower motor neuronopathy associated with renal cell carcinoma.

We describe a unique case of a patient with a reversible paraneoplastic motor neuronopathy who presented with hypercapnic respiratory failure. The patient developed progressive respiratory and limb muscle weakness until treated with removal of a renal cell carcinoma, which was followed by a complete resolution of neuromuscular symptoms. The literature of paraneoplastic motor neuronopathies is reviewed, specifically in reference to respiratory failure.

Outcome of severe brain injury: a multimodality neurophysiologic study.

We screened all head-injured trauma patients admitted to Lehigh Valley Hospital during a 2-year period. From 725 screened patients, 69 patients in a coma on the second day after trauma were entered into this study. During the first week, these patients underwent electroencephalography (EEG), evoked potentials, ocular pneumoplethysmography, and transcranial Doppler (TCD) sonography. Clinical examinations were undertaken 2 and 7 days after trauma. Test results were correlated with functional clinical outcome at 6 months. In a multiple regression analysis, EEG was the major independent variable that significantly predicted 6-month outcome based on Glasgow Outcome Scale score. Transcranial Doppler sonography contributed a small additional component. Though EEG was the most significant predictive factor in this neurophysiological battery, it did not add significantly to the predictive power of Glasgow Coma Scale score determined at day 7. These findings suggest that in neurophysiologic testing in this type of patient is not useful in improving predictive outcome data.

Differentiation of alpha coma from awake alpha by nonlinear dynamics of electroencephalography.

The electroencephalogram, as a probe of scalp-recorded electrical activity arising from the human cortex, provides useful information because of its temporal and spatial organization. Recent developments in nonlinear dynamics suggest that an object can be constructed in an n-dimensional space out of a temporal sequence of data such as an EEG signal and that its organization is characterized by the dimensionality of the object (in this case, human brain activity). We have carried out an analysis of a set of alpha coma EEG patterns in comparison to the awake alpha EEG patterns of normal volunteers and patients. Alpha coma recorded from a single channel is visually indistinguishable from normal resting alpha due to its similar frequency spectrum (a broad-band spectrum with 1/f characteristics). Our results show that alpha coma dimensionality, however, differs from that of normal alpha in that it has a greater variability over different temporal segments of EEG. Single channel recordings in 7 patients with alpha coma were differentiable from those of 10 subjects with "normal" EEGs. Through dynamic analysis of the EEG, novel methods of signal extraction from EEG may become evident and applicable to clinical practice.

Internal carotid artery redundancy is significantly associated with dissection.

BACKGROUND AND PURPOSE: Redundant internal carotid arteries have been considered a risk factor in tonsillectomy, adenoidectomy, and surgical treatment of peritonsillar abscess and also a potentially treatable cause of stroke. However, an association between internal carotid artery redundancy and spontaneous dissection has not yet been clearly demonstrated. METHODS: We reviewed, for spontaneous carotid artery dissection, records of all patients admitted to our institution during the period from 1986 through 1992 with the diagnosis of stroke or transient ischemic attack. We also reviewed 108 percutaneous cerebral arteriograms performed between September 1992 and December 1992 for presence of carotid artery redundancies. RESULTS: Thirteen patients exhibited spontaneous dissection. Of these, 8 of 13 (62%) patients and 13 of 20 (65%) internal carotid arteries, viewed to the siphon, had significant redundancies, kinks, coils, or loops. Of 108 consecutive arteriograms of patients without dissection, in which 187 internal carotid arteries were viewed to the siphon, there were 20 (19%) patients and 22 (12%) of 187 vessels with significant redundancy. Five patients in the dissection group and 2 in the nondissection group had bilateral internal carotid artery redundancy (P = .0019 and P = .0001, respectively). CONCLUSIONS: We found a significant correlation between internal carotid artery redundancy and dissection, particularly if redundancy is present bilaterally.

Primary angiitis of the central nervous system: unusual MR appearance.

The MR findings of a biopsy-proved case of primary angiitis of the central nervous system are described and compared with previously reported cases. Multiple punctate and linear areas of gadopentetate dimeglumine enhancement were present in the brain stem and white matter and appear to correspond to the inflammatory reaction of the small perforating vessels and perivascular tissues seen in the pathologic specimen.

Type III intermittency: a nonlinear dynamic model of EEG burst suppression.

Burst suppression electroencephalograms from 9 comatose patients have been studied using nonlinear dynamic techniques. These EEG records show many dynamical features characteristic of nonlinear systems, including sensitive dependence on initial conditions, self-organization, similarity across scales, and intermittency. Histograms of burst durations showed an asymmetric distribution with a decreasing tail of increasing duration. Interpreting the histograms from the standpoint of intermittency classifications of iterated dynamical maps, the absence of any conspicuous maximal cut-off duration suggests a type III intermittency. The power-law exponent of the decreasing tail is -3/2 for type III intermittency in the large scale sample size limit, and we have found the EEGs to be consistent with type III intermittency behavior. We have also developed a nonlinear algorithm which models burst suppression pattern based on a low dimensional return map. Burst suppression pattern appears to be the constrained activity of a nonlinear dynamical system at the transition to chaos.

Development of a novel EEG rating scale for head injury using dichotomous variables.

We developed a new EEG rating scale for electrographic assessment of head injured patients. Phenomena present in posttraumatic EEG were scored as dichotomous variables (present or absent). These phenomena included background activity (alpha, beta, theta, delta), sleep spindles, focal abnormalities, reactivity and variability, epileptiform activity, and specific comatose patterns. Each variable was weighted according to its perceived prognostic value: i.e., normal alpha 10, flat EEG -10, spindles 4, etc. Combinations of possible scores ranged from +23 to -10. Fifty-seven EEGs from different head injured patients were independently and retrospectively analyzed by two investigators. There was a high correlation for intra- (r = 0.95) and inter- (r = 0.85) observer rating using the dichotomous test. When patients with scores over 15 (i.e., with reactive alpha) and patients with scores of -10 (i.e., ECI records) were excluded, the intra-rater and inter-rater correlations were still high (0.81 and 0.76, respectively). There was a high correlation between Glasgow outcome score at discharge and the dichotomous EEG score. This EEG scale scores most major categories of EEG activity, utilizes a multipoint scale for correlation purposes, and allows data to be analyzed in sub-categories (i.e., spindles in coma). The separate weighting score allows for refinement of the scale after data collection (i.e., to fit prospective outcome). We feel that this scale is reproducible and valid, and may be applicable to other patient groups with severely altered EEGs.

Alzheimer's disease in Down's syndrome with SPECT.

Alzheimer's disease often occurs in patients with Down's syndrome. SPECT scanning with I-123 IMP and Tc-99m HMPAO identifies decreased cerebral perfusion and metabolism in these patients at lower cost. In this case, SPECT scanning revealed changes in Alzheimer's disease in a Down's syndrome patient.

A private practice model for teaching and research activities.

The majority of neurologists in the United States are in fee for service patient management, dividing their time between hospital and office based practice. Many have had subspecialty training or have had research experience. It is our belief that research should be a component of a neurologist's practice. This is particularly true for an assessment of outcome. In order to accomplish this, we have developed a system which includes patient management, teaching, and clinical research, within our fee for service model.

Episodic low-amplitude events: an under-recognized phenomenon in clinical electroencephalography.

In a series of 20 EEGs from 15 patients, well-defined brief attenuations occurred interspersed among the background activity. These episodic low-amplitude events (ELAEs) typically lasted 0.5-4 s. They were hemispheric or bisynchronous and occurred in patients with coma of various etiologies, including status epilepticus. The episodes of attenuation were brief and no bursts of activity were present, distinguishing this finding from burst-suppression. Prognosis was poor in the patients with coma due to entities other than status epilepticus. In the setting of status epilepticus, the prognosis depended on the etiology. This pattern may be an ictal phenomenon, or a product of waveform simplification. ELAEs are a manifestation of seriously abnormal EEG activity and correlate with a 50% mortality.

Post traumatic extracranial vertebral artery dissection with locked-in syndrome: a case with MRI documentation and unusually favourable outcome.

A patient with a right vertebral artery dissection occurring after minor head trauma progressed to a massive pontine infarction. An unusually favourable outcome and MRI imaging are discussed.

An unusual subacute progressive motor neuronopathy with myasthenia-like features.

The initial presentation and clinical course of this 60-year old woman suggested a diagnosis of myasthenia gravis. The subsequent development of tongue fasciculations and the lack of response to treatment made a diagnosis of amyotrophic lateral sclerosis (ALS) more likely despite the presence of conjugate gaze paresis and the absence of many of the typical clinical and electromyographic (EMG) findings seen in this condition. The pathological findings were consistent with either a motor neuronopathy or an unusual variant of ALS. We review the clinical and pathological features of this unusual case in this report.

The electroencephalogram in Alzheimer-type dementia. A sequential study correlating the electroencephalogram with psychometric and quantitative pathologic data.

As part of a longitudinal cohort study of dementia, 139 patients with Alzheimer's disease (dementia of the Alzheimer type, senile dementia of the Alzheimer type, and mixed type [ischemic score, 4 to 7]) and 148 age-matched control subjects were evaluated for electroencephalographic (EEG) abnormalities and their evolution. Electroencephalograms were significantly different in the two groups; EEGs worsened overall in the two groups during a period of one to four years, but most subjects showed no alteration in their EEGs. Some patients showed improvement in their EEG findings during the follow-up period. A strong correlation between EEG grade and psychometric scores was consistently found over sequential studies. In a subgroup of patients on whom autopsies were performed, morphometric neuron loss correlated significantly with EEG severity.

The EEG in Alzheimer type dementia: lack of progression with sequential studies.

Our findings dispel the commonly held belief that the EEG always worsens progressively in dementia of the Alzheimer's type. In a continuing cohort analytical study of dementia, 139 patients with Alzheimer's disease and 148 controls were studied for EEG abnormalities and progression. EEGs were read without knowledge of the previous EEGs or clinical condition, and classified according to the presence of diffuse delta or theta, bisynchronous spikes, projected activity, and focal activity. EEGs were significantly different in the two groups. EEG scores generally worsened over 1-4 years, but most of the subjects showed no alteration in their EEG scores. A few patients with Alzheimer's disease showed improvement of EEG findings.