Edvard Ehler

Mild Traumatic Brain Injury

Traumatic brain injury (TBI) is one among the most frequent neurological disorders. Of all TBIs 90% are considered mild with an annual incidence of 100–300/100 000. Intracranial complications of mild traumatic brain injury (MTBI) are infrequent (10%), requiring neurosurgical intervention in a minority of cases (1%), but potentially life threatening (case fatality rate 0.1%). Hence, a true health management problem exists because of the need to exclude the small chance of a life‐threatening complication in a large number of individual patients. The 2002 EFNS guideline used the best evidence approach based on the literature until 2001 to guide initial management with respect to indications for computed tomography (CT), hospital admission, observation and follow‐up of MTBI patients. This updated EFNS guideline for initial management in MTBI proposes a more selective strategy for CT when major [dangerous mechanism, Glasgow Coma Scale (GCS) < 15, 2 points deterioration on the GCS, clinical signs of (basal) skull fracture, vomiting, anticoagulation therapy, post‐traumatic seizure] or minor (age, loss of consciousness, persistent anterograde amnesia, focal deficit, skull contusion, deterioration on the GCS) risk factors are present based on published decision rules with a high level of evidence. In addition, clinical decision rules for CT now exist for children as well. Since 2001, recommendations, although with a lower level of evidence, have been published for clinical observation in hospitals to prevent and treat other potential threats to the patient including behavioural disturbances (amnesia, confusion and agitation) and infection.

Pramipexole and pergolide in the treatment of depression in Parkinson's disease:a national multicentre prospective randomized study.

An 8‐month multicentre prospective randomized study aimed at comparing the effects of dopamine receptor agonists pramipexole (PPX; Mirapexin®) and pergolide (PRG; Permax®) as add‐on to L‐dopa therapy on depression [Montgomery and Asberg Depression Rating Scale (MADRS)] in 41 non‐demented patients (25 men, 16 women) suffering from both mild or moderate depression and advanced Parkinsons disease (PD). The assessment was performed by a blinded independent observer. Motor symptoms (UPDRS III), motor complications (UPDRS IV), activities of daily living (UPDRS II and VI) and depressive symptoms as measured by Self – Rating Depression Scale by Zung were evaluated in an open‐label design.

A double-blind, randomized, placebo-controlled, parallel-group study of Sativex, in subjects with symptoms of spasticity due to multiple sclerosis

Abstract Background: Muscle spasticity is common in multiple sclerosis (MS), occurring in more than 60% of patients. Objective: To compare Sativex with placebo in relieving symptoms of spasticity due to MS. Methods: A 15-week, multicenter, double-blind, randomized, placebo-controlled, parallel-group study in 337 subjects with MS spasticity not fully relieved with current anti-spasticity therapy. Results: The primary endpoint was a spasticity 0–10 numeric rating scale (NRS). Intention-to-treat (ITT) analysis showed a non-significant improvement in NRS score, in favor of Sativex. The per protocol (PP) population (79% of subjects) change in NRS score and responder analyses (≥30% improvement from baseline) were both significantly superior for Sativex, compared with placebo: −1·3 versus −0·8 points (change from baseline, p=0·035); and 36% versus 24% (responders, p=0·040). These were supported by the time to response (ITT: p=0·068; PP: p=0·025) analyses, carer global impression of change assessment (p=0·013) and timed 10-meter walk (p=0·042). Among the subjects who achieved a ≥30% response in spasticity with Sativex, 98, 94 and 73% reported improvements of 10, 20 and 30%, respectively, at least once during the first 4 weeks of treatment. Sativex was generally well tolerated, with most adverse events reported being mild-to-moderate in severity. Discussion and conclusions: The 0–10 NRS and responder PP analyses demonstrated that Sativex treatment resulted in a significant reduction in treatment-resistant spasticity, in subjects with advanced MS and severe spasticity. The response observed within the first 4 weeks of treatment appears to be a useful aid to prediction of responder/non-responder status.

Highly unstable sequence interruptions of the CTG repeat in the myotonic dystrophy gene.

Myotonic dystrophy type 1 is caused by the expansion of a CTG repeat in the 3′ UTR of the DMPK gene. A length exceeding 50 CTG triplets is pathogenic. Intermediate alleles with 35–49 triplets are not disease‐causing but show instability in intergenerational transmissions. We report on the identification of multiple patients with different patterns of CCG and CTC interruptions in the DMPK CTG repeat tract that display unique intergenerational instability. In patients bearing interrupted expanded alleles, the location of the interruptions changed dramatically between generations and the repeats tended to contract. The phenotype for these patients corresponded to the classical form of the disease, but in some cases without muscular dystrophy and possibly with a later onset than expected. Symptomatic patients bearing interrupted intermediate length repeat tracts were also identified, although the role of the interruptions in their phenotype remains unclear. The identification of interruptions in the DMPK repeat has important consequences for molecular genetic testing where they can lead to false negative conclusions.

A double-blind, randomized, placebo-controlled, parallel group study of THC/CBD spray in peripheral neuropathic pain treatment

Peripheral neuropathic pain (PNP) associated with allodynia poses a significant clinical challenge. The efficacy of Δ9‐tetrahydrocannabinol/cannabidiol (THC/CBD) oromucosal spray, a novel cannabinoid formulation, was investigated in this 15‐week randomized, double‐blind, placebo‐controlled parallel group study.

Cognitive performance in people with Parkinson's disease and mild or moderate depression: effects of dopamine agonists in an add‐on to l‐dopa therapy

In a randomized prospective multi‐centre study, we evaluated the cognitive performances of a group of 41 non‐demented patients, all with advanced Parkinsons disease (PD) and a current depressive episode, in whom the effects of pramipexole (PPX) and pergolide (PRG) in an add‐on to l‐dopa therapy were also studied and published with regard to motor symptoms of PD, motor complications and depression. The Trail Making Test, the Stroop test and four subtests (arithmetic, picture completion, digit symbols and similarities) of the Wechsler Adult Intelligence Scale‐Revised were performed prior to and 8 months after the administration of either PPX or PRG. We found no statistically significant difference between the two tested drugs or between the first and the last visit in any of the above‐listed neuropsychological tests. All patients’ motor outcomes significantly improved and we conclusively demonstrated the anti‐depressive effect of PPX. The dissociation of dopaminomimetic effects on the different tested domains indicates that there are different pathological mechanisms of cognitive, motor and affective disturbances in advanced PD patients. In our non‐demented group of fluctuating depressed PD subjects, both PPX and PRG administration in combination with l‐dopa were safe in terms of the effect on cognitive performance.

Myasthenia gravis, castleman disease, pemphigus, and anti-phospholipid syndrome

Introduction: Myasthenia gravis is an autoimmune disease marked by neuromuscular transmission failure at the neuromuscular junction. Castleman disease is a rare lymphoproliferative disease characterized by non‐cancerous angiofolicular hyperplasia of lymphatic tissue. Methods and results: We describe a young man with rapid, successive manifestations of myasthenia gravis, a solitary form of Castleman disease, pemphigus vulgaris, and anti‐phospholipid syndrome, which resulted in 2 ischemic cerebrovascular events that caused a severe central neurological deficit. Discussion: We were unable to find a similar case in the literature, but we hypothesize that the temporal concidence of these clinical entities may be related to a common immunological pathway, such as B‐cell activation. Therefore, we treated the patient with an immunosuppressant and anticoagulant treatment, as well as rituximab, a monoclonal antibody therapy against CD20+. Muscle Nerve 47:447‐451, 2013

Efficacy and safety of abobotulinumtoxinA liquid formulation in cervical dystonia: A randomized-controlled trial.

Approved botulinum toxin A products require reconstitution. AbobotulinumtoxinA solution for injection is a ready‐to‐use liquid formulation of abobotulinumtoxinA.

Stiff-person syndrome following tick-borne meningoencephalitis.

Stiff-person syndrome (SPS) is a rare disorder characterized by muscle stiffness and painful spasms. Misdiagnosis may occur due to the fact that the clinical picture of SPS is often atypical. The main pathophysiologic mechanism underlying the development of SPS is insufficient inhibition at the cortical and spinal levels. There is good evidence for a primary autoimmune etiology. A 61-year-old man was admitted to a neurological department due to muscle hypertonia with episodic attacks of painful spasms predominantly affecting axial muscles. The symptoms developed shortly after tickborne meningoencephalitis. Electromyography (EMG) revealed signs of continuous motor unit activity. Antibodies against glutamate decarboxylase (anti-GAD) were highly elevated. We present a case of a man who developed clinically severe anti-GAD positive SPS, provoked by tick-borne encephalitis. After therapeutic plasma exchange (TPE) a rapid, temporary improvement of the clinical and neurophysiological findings was noted. Only after being placed on long-term immunosuppression did the patient achieve stable recovery. This case supports the importance of EMG findings and demonstrates the effect of TPE as well as the need for chronic immunosuppression in severe cases of SPS.

Changes of Retina Are Not Involved in the Genesis of Visual Hallucinations in Parkinson’s Disease

Parkinsons disease (PD) is characterized by motor and nonmotor symptoms. Nonmotor symptoms include primarily visual hallucinations (VH). The aim of our study was to establish whether patients with PD and visual hallucinations (PDH+) have structural changes of retina detected by an optical coherence tomography (OCT) in comparison with PD patients without visual hallucinations (PDH−). We examined 52 PD patients (18 with VH, 34 without VH) and 15 age and sex matched healthy controls. Retinal nerve fiber layer (RNFL) thickness and macular thickness and volume were assessed by OCT. Functional impairment of retina was assessed using 2.5% contrast sensitivity test. For OCT outcomes we analyzed 15 PDH+ and 15 PDH− subjects matched for age, gender, and PD duration. For contrast sensitivity we analyzed 8 pairs of patients matched for age, gender, and visual acuity. There was no significant difference in RNFL thickness and macular thickness and macular volume between 15 PDH+ and 15 PDH− subjects, and also between a group of 44 PD patients (both PDH+ and PDH−) and 15 age and gender matched healthy controls. No significant difference was found for 2.5% contrast sensitivity test values between PDH+ and PDH− subjects. Therefore we conclude that functional and structural changes in retina play no role in genesis of VH in PD.