Alan Weintraub

A randomized trial of modafinil for the treatment of fatigue and excessive daytime sleepiness in individuals with chronic traumatic brain injury.

BackgroundThis study examines the efficacy of modafinil in treating fatigue and excessive daytime sleepiness in individuals with traumatic brain injury (TBI). MethodsA single-center, double-blind, placebo-controlled cross-over trial, where 53 participants with TBI were randomly assigned to receive up to 400 mg of modafinil, or equal number of inactive placebo tablets. Main eligibility criteria were being at least 1 year post-TBI severe enough to require inpatient rehabilitation. The primary outcome measures were fatigue (Fatigue Severity Scale, FSS) and daytime sleepiness (Epworth Sleepiness Scale, ESS). ResultsAfter adjusting for baseline scores and period effects, there were no statistically significant differences between improvements seen with modafinil and placebo in the FSS at week 4 (–0.5 ± 1.88; P = .80) or week 10 (–1.4 ± 2.75; P = .61). For ESS, average changes were significantly greater with modafinil than placebo at week 4 (–1.2 ± 0.49; P = .02) but not at week 10 (–0.5 ± 0.87; P = .56). Modafinil was safe and well tolerated, although insomnia was reported significantly more often with modafinil than placebo (P = .03). ConclusionsWhile there were sporadic statistically significant differences identified, a clear beneficial pattern from modafinil was not seen at either week 4 or week 10 for any of the 12 outcomes. There was no consistent and persistent clinically significant difference between treatment with modafinil and placebo.

Magnetic resonance imaging of traumatic brain injury: relationship of T2 SE and T2*GE to clinical severity and outcome

Primary objectives: To evaluate (1) the sensitivity of magnetic resonance imaging (MRI) T2* weighted gradient echo (GE) vs T2 weighted spin echo (SE) technology for lesion detection in traumatic brain injury (TBI) and (2) the relationship of lesion patterns to acute clinical severity and 1 year post-injury outcome measures. Research design: Comparative analysis. Methods and procedures: Forty-three acute rehabilitation patients with TBI were imaged utilizing T2 SE and T2* GE techniques an average of 26 days post-injury. Acute clinical severity measures, including Glasgow Coma Scale (GCS), time to follow commands (TFC) and post-traumatic amnesia (PTA) were abstracted from medical records. One-year post-injury outcome measures including Glasgow Outcome Scale (GOS), Disability Rating Scale (DRS) and the Craig Handicap Assessment and Reporting Technique—Short Form (CHART-SF) were collected as part of a comprehensive annual follow-up. Main outcomes and results: In comparison to T2 SE, T2* GE more frequently detected lesions in each of the cortical (p < 0.0001), white matter (p < 0.001), central grey (p < 0.001) and brainstem (p < 0.01) regions and in each of the frontal (p < 0.0001), temporal (p < 0.0001), parietal (p < 0.001) and occipital (p < 0.0001) lobes. With regards to acute clinical severity measures, T2* GE findings were the best predictors of GCS and the only significant predictors of PTA, while T2 SE findings were better predictors of TFC. For 1 year post-injury outcome measures, multivariate regression models utilizing T2 SE and T2* GE findings in combination were the best predictors of DRS and GOS and T2 SE findings alone were the best predictors of CHART-SF. Conclusions: This study demonstrates the enhanced sensitivity of T2* GE for detecting haemorrhagic lesions associated with TBI and supports a complimentary role for both T2 SE and T2* GE weighted imaging in characterizing injury severity and predicting longer-term outcomes.

Natural History of Headache Five Years after Traumatic Brain Injury

Headache is one of the most frequently reported symptoms following traumatic brain injury (TBI). Little is known about how these headaches change over time. We describe the natural history of headache in individuals with moderate to severe TBI over 5 years after injury. A total of 316 patients were prospectively enrolled and followed at 3, 6, 12, and 60 months after injury. Individuals were 72% male, 73% white, and 55% injured in motor vehicle crashes, with an average age of 42. Pre-injury headache was reported in 17% of individuals. New or worse headache prevalence remained consistent with at least 33% at all time points. Incidence was >17% at all time points with first report of new or worse headache in 20% of participants at 60 months. Disability related to headache was high, with average headache pain (on 0-10 scale) ranging from 5.5 at baseline to 5.7 at 60 months post-injury, and reports of substantial impact on daily life across all time points. More than half of classifiable headaches matched the profile of migraine or probable migraine. Headache is a substantial problem after TBI. Results suggest that ongoing assessment and treatment of headache after TBI is needed, as this symptom may be a problem up to 5 years post-injury.

Posttraumatic Hydrocephalus as a Confounding Influence on Brain Injury Rehabilitation: Incidence, Clinical Characteristics, and Outcomes.

OBJECTIVE To describe incidence, clinical characteristics, complications, and outcomes in posttraumatic hydrocephalus (PTH) after traumatic brain injury (TBI) for patients treated in an inpatient rehabilitation program. DESIGN Cohort study with retrospective comparative analysis. SETTING Inpatient rehabilitation hospital. PARTICIPANTS All patients admitted for TBI from 2009 to 2013 diagnosed with PTH (N=59), defined as ventriculomegaly, delayed clinical recovery discordant with injury severity, hydrocephalus symptoms, or positive lumbar puncture results. INTERVENTIONS None. MAIN OUTCOME MEASURES Primary measures were incidence of PTH and patient and injury characteristics. Secondary measures included frequency and timing of ventriculoperitoneal (VP) shunt, related complications, emergence from and duration of posttraumatic amnesia (PTA), Rancho Los Amigos Scale (RLAS) score, and FIM score at rehabilitation admission and discharge. RESULTS Of 701 patients with TBI admitted, 59 (8%) were diagnosed with PTH. Of these, the median age was 25 years, with 73% being men. At initial presentation, 52 (88%) did not follow commands. Fifty-two (90%) patients with PTH had a VP shunt placed. Median time from injury to shunt placement was 69 (range, 9-366) days. Seven (12%) patients with PTH experienced postsurgical seizure, 3 (6%) had shunt infection, and 7 (12%) had shunt malfunction. Thirty-six (61%) patients with PTH emerged from PTA during rehabilitation. Median total FIM score at rehabilitation admission was 20 (range, 18-76), and at discharge it was 43 (range, 18-118). Injury severity predicted outcome at rehabilitation admission, whereas shunt timing predicted outcome at rehabilitation discharge. CONCLUSIONS Incidence of PTH was observed in 8% of patients with TBI in inpatient rehabilitation. Earlier shunting predicted improved outcome during rehabilitation. Future studies should prospectively examine clinical decision rules, type, and timing of intervention and the coeffectiveness of rehabilitation treatment on outcomes.

A new prism use for treatment of cyclo-deviation in trochlear nerve injury.

Visual problems are common in patients with severe TBI. Diplopia is among the most frustrating of visual disturbances for patients, due to its functional consequences. This is further compounded by often slow, and at times, incomplete or partial recovery over six months or longer. Ocular cranial nerve injuries (particularly trochlear nerve) occur in 0.2%-1.4% of severe TBI patients. This paper presents a new prism treatment application for treating rotational diplopia arising from Trochlear nerve injury.

Impact of timing of ventriculoperitoneal shunt placement on outcome in posttraumatic hydrocephalus

OBJECTIVE Posttraumatic hydrocephalus (PTH) is a frequent sequela of traumatic brain injury (TBI) and complication of related cranial surgery. The roles of PTH and the timing of cerebrospinal fluid (CSF) shunt placement in TBI outcome have not been well described. The goal of this study was to assess the impact of hydrocephalus and timing of ventriculoperitoneal (VP) shunt placement on outcome during inpatient rehabilitation after TBI. METHODS In this cohort study, all TBI patients admitted to Craig Hospital between 2009 and 2013 were evaluated for PTH, defined as ventriculomegaly, and hydrocephalus symptoms, delayed or deteriorating recovery, or elevated opening pressure on lumbar puncture. Extent of ventriculomegaly was quantified by the Evans index from CT scans. Outcome measures were emergence from and duration of posttraumatic amnesia (PTA) and functional status as assessed by means of the Functional Independence Measure (FIM). Findings in this group were compared to findings in a group of TBI patients without PTH (controls) who were admitted for inpatient rehabilitation during the same study period and met specific criteria for inclusion. RESULTS A total of 701 patients were admitted with TBI during the study period. Of these patients, 59 (8%) were diagnosed with PTH and were included in this study as the PTH group, and 204 who were admitted for rehabilitation and met the criteria for inclusion as controls constituted the comparison group (no-PTH group). PTH was associated with initial postinjury failure to follow commands, midline shift or cistern compression, subcortical contusion, and craniotomy or craniectomy. In multivariable analyses, independent predictors of longer PTA duration and lower FIM score at rehabilitation discharge were PTH, emergency department Glasgow Coma Scale motor score < 6, and longer time from injury to rehabilitation admission. PTH accounted for a 51-day increase in PTA duration and a 29-point reduction in discharge FIM score. In 40% of PTH patients with preshunt CT brain imaging analyzed, ventriculomegaly (Evans index > 0.3) was observed 3 or more days before VP shunt placement (median 10 days, range 3-102 days). Among PTH patients who received a VP shunt, earlier placement was associated with better outcome by all measures assessed and independently predicted better FIM total score and shorter PTA duration. CONCLUSIONS Posttraumatic hydrocephalus predicts worse outcome during inpatient rehabilitation, with poorer functional outcomes and longer duration of PTA. In shunt-treated PTH patients, earlier CSF shunting predicted improved recovery. These results suggest that clinical vigilance for PTH onset and additional studies on timing of CSF diversion are warranted.

Comment on The Decision to Provide Testosterone Supplementation to Patients With Traumatic Brain Injury

To the Editor, We read with interest the article, “The Decision to Provide Testosterone Supplementation in Patients With Traumatic Brain Injury,” [1] published in the November issue of this journal. In this article, warning is expressed by the authors that “an acute change in mental status including but not limited to aggressiveness, motor restlessness, cognitive decline, and paranoia after beginning steroid supplementation should alert the clinician to a hormonal cause of the mental status change,” suggesting that it is their belief that the patient’s increased agitation was definitively linked to testosterone supplementation. The incidence of hypogonadism in men after severe traumatic brain injury is approximately 30% [2]. We have been conducting a prospective, placebo-controlled clinical trial of testosterone (T) therapy for men who exhibit hypogonadism (low testosterone, defined as a serum T <260 ng/dL) after traumatic brain injury. To date we have had only 1 adverse event related to aggressive behavior from among 36 participants, and that individual was in the normal testosterone control group (ie, individuals with normal testosterone who are not receiving any treatment or placebo). As serum assessment of the patient’s endocrine status in the case report was not performed during the period of agitation, there is no way to know what the underlying mechanism of this patient’s agitation was, or whether it was related to his hormone status at all. It appears that the patient’s T level was normal at the time of initiation of T therapy, which would suggest that he was not hypogonadal. Although we acknowledge that testosterone therapy, if given to men who are not hypogonadal, or in high doses, can be associated with adverse events [3], we disagree that physiologic T therapy to correct hypogonadal men to normal T levels would do so. We agree with the authors that a careful risk-benefit analysis should be performed before initiation of testosterone therapy, but we caution against the generalization of their conclusions to indicate that testosterone supplementation is contraindicated in all patients with TBI.

Terson's Syndrome Managed with 25-Gauge Vitrectomy.

Tersons Syndrome represents vitreous hemorrhage due to intracranial hemorrhage. A series of 18 adult eyes with Tersons Syndrome, due to either traumatic brain injury or ruptured aneurysm, successfully managed with 25-gauge vitrectomy was reported. All patients had improved vision, although some had limitation due to effects of surgery or the underlying pathology.