Carol J. Schramke

Short-term prognosis in early relapsing-remitting multiple sclerosis

Objective: To characterize a group of patients with early MS using prognostic factors and to determine whether these prognostic factors impact on short-term prognosis. Methods: Data were collected prospectively on 98 patients newly diagnosed with MS in our MS clinic between 1990 and 1998 (average follow-up, 37 months from the time of onset of clinically definite MS [CDMS]). Six prognostic factors were recorded: age at onset, symptoms at onset, MRI status at onset and at diagnosis of CDMS, interval between the first and second attack, attack frequency in the first 2 years, and completeness of recovery from initial attacks. Completeness of recovery was determined using Expanded Disability Status Scale scores (EDSS). Progression was determined by final EDSS and changes in EDSS between initial presentation and final follow-up. Results: Patients predicted to have low risk of progression of MS based on the prognostic factors represented 17% of our patient population (0 to 1 risk factor for progression). The patients with high risk of progression (4 to 6 risk factors) represented 24% of patients. Patients with a high number of risk factors did significantly worse than those with a small or medium number of risk factors in terms of final EDSS and progression to higher EDSS. At the time of diagnosis of CDMS, MRI findings suggestive of MS were seen in 84% of patients (suspicious in 13%, negative in 3%). Conclusion: Short-term prognosis was influenced by the presence or absence of a high number of these six risk factors.

Ketamine use in the treatment of refractory status epilepticus

Refractory status epilepticus (RSE) occurs when status epilepticus (SE) fails to respond to appropriate therapy with typical antiepileptic drugs (AEDs). Animal studies have shown ketamine to be a highly efficacious agent in this setting, but very few case reports describe use of ketamine in human SE or RSE. We report a retrospective review of 11 patients who were treated for RSE with ketamine infusion in addition to other standard AEDs over a nine-year period. Data collection included age, gender, history of epilepsy, etiology of RSE, daily dose of ketamine, co-therapeutic agents, duration of seizures, treatment response, and disposition. RSE was successfully terminated in all 11 patients treated with ketamine. Dosing ranged from 0.45 mg/kg/h to 2.1 mg/kg/h based upon the preference of the treating clinician and response to therapy, with maximal daily doses ranging from 1392 mg to 4200 mg. Ketamine was the last AED used prior to resolution of RSE in 7/11 (64%) cases. In the remaining four cases, one other AED was added after ketamine infusion had begun. Time from ketamine initiation to seizure cessation ranged from 4 to 28 days (mean=9.8, SD=8.9). In 7/11 patients, RSE was resolved within one week of starting therapy. Administration of ketamine was uniformly associated with improvement in hemodynamic stability. Six of the seven patients (85%) who required vasopressors during early treatment for RSE were able to be weaned from vasopressors during ketamine infusion. No acute adverse effects were noted. These findings suggest that ketamine may be a safe and efficacious adjunctive agent in the treatment of RSE.

Poor recovery after the first two attacks of multiple sclerosis is associated with poor outcome five years later

OBJECTIVE Examine the relative importance of several risk factors for progression, in a large sample of MS patients. METHODS Using a retrospective design in a single university-based MS treatment center, we studied 207 patients with relapsing remitting MS diagnosed, treated at our center, evaluated within one year of their second attack, and at least 2 years after their first attack. Risk factors were: 1) age greater than 40 at first attack; 2) more than 2 attacks in the 2 years from onset; 3) EDSS >1.5 after second attack (poor recovery); 4) male gender; and 5) motor symptoms at onset. Groups were defined as having a few (0 to 2) or many (3 to 5) risk factors. RESULTS Two hundred seven patients were followed for an average of 94 months (SD=44). 30% were over 40 years of age at onset, 38% had more than 2 attacks in 2 years, 28% had an EDSS >1.5 after the second attack (i.e., had poor recovery), 24% were male, and 58% had motor symptoms at onset. Regression analysis and Kaplan-Meier survival curves that suggested poor recovery after the first two attacks were the best individual predictors of progression at 5 years after initial diagnosis. In addition, having many individual risk factors was associated with having a higher risk of progression (p<.001 by Mann Whitney U, sustained final EDSS at an average disease duration of 9.7 years). CONCLUSIONS This study suggests a paramount importance of recovery from early attacks, as well as an additive effect of individual risk factors for progression of MS in the first several years after diagnosis.

The efficacy of topiramate in adult refractory status epilepticus: Experience of a Tertiary Care Center

Refractory status epilepticus (RSE) occurs in patients with SE when they fail to respond to traditional medical therapy. Because there are very few case reports of topiramate (TPM) treatment of RSE in adult patients, we examined our experience with TPM with regard to its safety and efficacy in seizure termination in RSE in an adult patient population. We report a retrospective review of 35 adult patients with RSE who were treated with TPM in addition to other antiepileptic drugs (AEDs) between 2003 and 2010. After failure of initial treatments of benzodiazepines and weight-based intravenous loading doses of standard AEDs, TPM tablets were crushed and administered via nasogastric tube. Data were collected on age, gender, history of epilepsy, etiology of RSE, daily dose of TPM, co-therapeutic agents, treatment response, and disposition. Following initiation of TPM use and discontinuation of continuous intravenous anesthetics with no additional AEDs administered, cumulative cessation of RSE in patients was 4/35 (11%) at one day, 10/35 (29%) at two days, and 14/35 (40%) at three days. However, when including all patients and comparing the two patient groups in which RSE was or was not terminated within three days of initiating TPM as the last or not last AED given, there was no significant difference. Time to TPM response was not associated with the type of seizures, etiology of SE, or whether there was a history of epilepsy. There were no documented side effects or complications of therapy with TPM. This study provides support for the use of TPM as an adjunctive agent in the treatment of RSE.

Neurosarcoidosis mimicry of multiple sclerosis: clinical, laboratory, and imaging characteristics.

Objective To characterize the clinical and laboratory features of neurosarcoidosis (NS), presenting with findings consistent with multiple sclerosis (MS). Methods Retrospective chart review of our entire NS database was undertaken. Patients initially diagnosed with MS but who were subsequently diagnosed as having both systemic and neurologic sarcoidosis years later were selected for more detailed review. Results Seven patients were identified who were diagnosed with MS (although only 4 of these met McDonald criteria for MS during chart review) and 1 patient with optic neuritis who had a diagnosis of likely MS. These patients maintained the diagnosis of MS for a mean of 107 months (median 50 mo, range 23 to 262 mo) before the diagnosis was changed to NS, concomitant with the discovery of biopsy-proven systemic sarcoidosis in 4 cases. Neurologic manifestations included relapsing-remitting optic neuritis, myelopathy, dystonic spasms, sensory abnormalities, paraparesis, and hemiparesis. Patients appeared to improve or stabilize by treatment with corticosteroids or alternative immunosuppressants. MRIs demonstrated rounded or ovoid periventricular white matter changes typical for MS. Conclusion Patients with NS are frequently diagnosed initially with MS because of a considerable overlap of clinical and laboratory features. However, due to the relative rarity of NS, a misdiagnosis of NS as MS occurred only infrequently in our MS clinic.

Using the Minnesota Multiphasic Inventory 2, EEGs, and clinical data to predict nonepileptic events

Minnesota Multiphasic Inventory 2 (MMPI-2) scale 3, duration of illness, and routine EEGs have been used to predict nonepileptic events (NEEs) with a high degree of accuracy in patients referred for video/EEG (vEEG) monitoring. This study tested the Storzbach logistic regression equation in our patients with definitive epileptic seizures (n=57) or NEEs without evidence of epileptiform activity (n=51) during vEEG monitoring, yielding an overall classification accuracy of 81%, sensitivity of 80%, and specificity of 81%. This study also replicated previous findings of significant group differences in duration (years) of spells, number of elevations on the MMPI-2, MMPI-2 elevations on scales 1, 2, 3, and 8, and incidence of the conversion valley on the MMPI-2. Our findings indicated that combined use of the MMPI-2 and clinical variables was most predictive of patients with NEEs.

Using patient history to distinguish between patients with non-epileptic and patients with epileptic events

Information obtained during psychological evaluations of 93 patients with epileptic events (EEs) and 63 with nonepileptic events (NEEs) was used to test the relative contributions of multiple risk factors to prediction of NEEs during video/EEG monitoring. The best group of independent predictors of NEEs comprised: (1) age at first spell, (2) symptoms of a psychiatric diagnosis other than anxiety or depression, (3) marital instability, (4) symptoms of an anxiety disorder other than panic disorder, and (5) years of education. Report of childhood abuse or neglect and taking psychotropic medication correlated with most of the other risk factors for NEEs. It may not be necessary to gather data on all of the variables shown to be associated with NEEs. Although there is a high prevalence of risk factors for psychopathology in patients with EEs, it is lower compared with that of patients with NEEs, and patients with EEs are less likely to report multiple risk factors.

Sample size estimates for determining treatment effects in high-risk patients with early relapsing-remitting multiple sclerosis.

Background: Risk factors for short-term progression in early relapsing-remitting MS have been identified recently. Previously we determined potential risk factors for rapid progression of early relapsing-remitting MS and identified three groups of high-risk patients. These non-mutually exclusive groups of patients were drawn from a consecutively studied sample of 98 patients with newly diagnosed MS. High-risk patients had a history of either poor recovery from initial attacks, more than two attacks in the first two years of disease, or a combination of at least four other risk factors. Objective: To determine differences in sample sizes required to show a meaningful treatment effect when using a high-risk sample versus a random sample of patients. Methods: Power analyses were used to calculate the different sample sizes needed for hypothetical treatment trials. Results: We found that substantially smaller numbers of patients should be needed to show a significant treatment effect by employing these high-risk groups of patients as compared to a random population of MS patients (e.g., 58% reduction in sample size in one model). Conclusion: The use of patients at higher risk of progression to perform drug treatment trials can be considered as a means to reduce the number of patients needed to show a significant treatment effect for patients with very early MS.

Specific clinical phenotypes in relapsing multiple sclerosis: The impact of relapses on long-term outcomes

OBJECTIVE The impact of relapses on the disease course of relapsing MS remains to be determined. This study aims to identify and characterize clinical phenotypes of relapse onset MS in a longitudinally studied cohort. METHODS We recorded the clinical course of MS during the first decade of disease, using five-year epochs. Patients were stratified as: no worsening due to relapse or secondary progression (type A), relapse with worsening seen without secondary progression (type B), secondary progression with no worsening due to relapse (type C), worsening due to relapses mixed with secondary progression (type D). RESULTS Of 176 patients followed from diagnosis for 12.62 ± 4.18 years, 93.2% (164/176) had increased disability in their first 5-year epoch of MS and 52.2% (72/138) in the next. The phenotypes significantly differed by EDSS change during each epoch (p<0.001), final confirmed MSSS (p ≤ 0.002) and relapse rate (p<0.001). Type D fared worse than others by change in EDSS and MSSS. CONCLUSION We identified multiple specific phenotypes of MS and temporal shifts between phenotypes according to relapse type and progression.

Comparison of psychosocial factors between patients with benign fasciculations and those with amyotrophic lateral sclerosis.

In this retrospective study, we compared the initial presentation of patients who were eventually diagnosed with either benign fasciculations (BF) or amyotrophic lateral sclerosis (ALS). We found a significantly higher number of patients with BF reporting a past history of psychiatric symptoms, life stressors, and concurrent psychosomatic symptoms. There was no difference between the two groups in patient report of current anxiety or depression symptoms. These findings support our hypothesis that BF are a manifestation of psychological distress due to somatization and that reviewing psychosocial history is important when patients are being evaluated for fasciculations. Patients seeking medical attention for fasciculations and who do not report a history of underlying psychiatric or psychosomatic disorders should be followed closely as fasciculations have been reported to be a presenting feature of ALS.