Brain Connectivity and Network Analysis in Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with no effective treatment or cure. ALS is characterized by the death of lower motor neurons (LMNs) in the spinal cord and upper motor neurons (UMNs) in the brain and their networks. Since the lower motor neurons are under the control of UMN and the networks, cortical degeneration may play a vital role in the pathophysiology of ALS. These changes that are not apparent on routine imaging with CT scans or MRI brain can be identified using modalities such as diffusion tensor imaging, functional MRI, arterial spin labelling (ASL), electroencephalogram (EEG), magnetoencephalogram (MEG), functional near-infrared spectroscopy (fNIRS), and positron emission tomography (PET) scan. They can help us generate a representation of brain networks and connectivity that can be visualized and parsed out to characterize and quantify the underlying pathophysiology in ALS. In addition, network analysis using graph measures provides a novel way of understanding the complex network changes occurring in the brain. These have the potential to become biomarker for the diagnosis and treatment of ALS. This article is a systematic review and overview of the various connectivity and network-based studies in ALS.

Clinical Evaluation and Treatment of Patients with Postconcussion Syndrome.

Postconcussion syndrome (PCS) is a complex set of symptoms occurring in a small percentage of patients following concussion. The condition is characterized by headaches, dizziness, cognitive difficulties, somatosensory issues, and a variety of other symptoms with varying durations. There is a lack of objective markers and standard treatment protocols. With the complexity created by premorbid conditions, psychosomatic issues, secondary gains, and litigations, providers often find themselves in a tough situation in the care of these patients. This article combines literature review and clinical insights with a focus on the underlying pathophysiology of PCS to provide a roadmap for evaluating and treating this condition.

Electricity, Neurology, and Noninvasive Brain Stimulation: Looking Back, Looking Ahead.

Electricity and neurology evolved synchronously over the past few centuries. This article looks at their origins and their journey into noninvasive brain stimulation technique of transcranial direct current stimulation (tDCS), which is now popular in neuroscience research.

Into a Shaking Limbo: Case Report of a Nonneoplastic Limbic Encephalitis with Faciobrachial Dystonic Seizures and Parkinsonism.

This case report describes a rare but classic presentation of a non-paraneoplastic, antibody-mediated limbic encephalitis. The clinical course did put us in a limbo as it evolved from seizure to Parkinsonism and then from metastasis to stroke, before it finally announced itself by its pathognomonic finding. Knowledge of this rare condition is important as early identification and treatment can change the course.

Clinical Evaluation of Patients with Vestibular Dysfunction.

Dizziness is a common reason for outpatient neurology consultation. Oftentimes, a complete workup by general practitioner, including MRI brain fails to reveal a cause. Some patients would have also undergone an ENT evaluation before approaching neurology for an answer. Such scenarios provide a challenge as well as opportunity for the neurologist to exercise their knowledge and clinical skills in arriving at a diagnosis. Conditions like 'Unspecified Vestibular Dysfunction' and 'Presbyvertigo' are often the underlying causes, which are either not recognized or misdiagnosed as BPPV, psychogenic or perceptive dizziness. This article's goal is to help understand vestibular system and diagnose vestibular dysfunction in clinical practice.

Comparison of costs and outcomes of patients presenting with a rare brainstem syndrome.

In this case report we compare two patients presenting with similar symptoms of a brainstem syndrome including ataxia, dysarthria, and diplopia. Their MRIs showed hyperintense FLAIR signal changes with patchy areas of contrast enhancement within the brainstem particularly the pons and cerebellum. The broad differential diagnosis of this brainstem pathology included rhomboencephalitis, neurosarcoidosis, lymphoma, vasculitis, infection, and paraneoplastic or autoimmune process. Patient 1 had an extensive work up including CSF cytology, MRI brain spectroscopy, full body CT, cerebral angiogram, and ultimately brainstem biopsy. None of these studies were diagnostic of a specific etiology and total cost was $176,069. After months of declining medical condition without a clear diagnosis, chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) was considered and the patient began steroid therapy resulting in clinical and radiographic improvement. Patient 2 had serum and CSF studies that were negative for infectious, paraneoplastic, and other inflammatory processes. The team diagnosed CLIPPERS and initiated steroid therapy within days resulting in dramatic clinical and radiographic resolution. The workup cost $12,905. Comparison of these cases shows how early awareness of CLIPPERS and a directed diagnostic work up can limit invasive diagnostic testing, expedite initiation of effective therapy, improve patient outcomes, and reduce cost.

Late Occurrence of PML in a Patient Treated for Lymphoma with Immunomodulatory Chemotherapies, Bendamustine, Rituximab, and Ibritumomab Tiuxetan.

PML caused by John Cunningham (JC) virus is a rare but an increasingly recognized entity. With the advent of newer immunomodulatory therapies with monoclonal antibodies, there is an increasing incidence of PML. Initially concern was restricted to patients treated for multiple sclerosis with natalizumab but more case reports are being reported during treatment for other conditions like Crohn's disease and lymphoma with agents such as rituximab. We report the case of a 66-year-old woman who developed PML a year after completion of therapy with rituximab, ibritumomab, and bendamustine.

Optimizing recovery potential through simultaneous occupational therapy and non-invasive brain-stimulation using tDCS.

PURPOSE: It is thought that following a stroke the contralesional motor region exerts an undue inhibitory influence on the lesional motor region which might limit recovery. Pilot studies have shown that suppressing the contralesional motor region with cathodal transcranial Direct Current Stimulation (tDCS) can induce a short lasting functional benefit; greater and longer lasting effects might be achieved with combining tDCS with simultaneous occupational therapy (OT) and applying this intervention for multiple sessions. METHODS: We carried out a randomized, double blind, sham controlled study of chronic stroke patients receiving either 5 consecutive days of cathodal tDCS (for 30 minutes) applied to the contralesional motor region and simultaneous OT, or sham tDCS+OT. RESULTS: we showed that cathodal tDCS+OT resulted in significantly more improvement in Range-Of-Motion in multiple joints of the paretic upper extremity and in the Upper-Extremity Fugl-Meyer scores than sham tDCS+OT, and that the effects lasted at least one week post-stimulation. Improvement in motor outcome scores was correlated with decrease in fMRI activation in the contralesional motor region exposed to cathodal stimulation. CONCLUSIONS: This suggests that cathodal tDCS combined with OT leads to significant motor improvement after stroke due to a decrease in the inhibitory effect that the contralesional hemisphere exerts onto the lesional hemisphere.

Transcranial direct current stimulation in stroke recovery.

Transcranial direct current stimulation (TDCS) is an emerging technique of noninvasive brain stimulation that has been found useful in examining cortical function in healthy subjects and in facilitating treatments of various neurologic disorders. A better understanding of adaptive and maladaptive poststroke neuroplasticity and its modulation through noninvasive brain stimulation has opened up experimental treatment options using TDCS for patients recovering from stroke. We review the role of TDCS as a facilitator of stroke recovery, the different modes of TDCS, and the potential mechanisms underlying the neural effects of TDCS.

Transcranial direct current stimulation: a noninvasive tool to facilitate stroke recovery.

Electrical brain stimulation, a technique developed many decades ago and then largely forgotten, has re-emerged recently as a promising tool for experimental neuroscientists, clinical neurologists and psychiatrists in their quest to causally probe cortical representations of sensorimotor and cognitive functions and to facilitate the treatment of various neuropsychiatric disorders. In this regard, a better understanding of adaptive and maladaptive plasticity in natural stroke recovery over the last decade and the idea that brain polarization may modulate neuroplasticity has led to the use of transcranial direct current stimulation (tDCS) as a potential enhancer of natural stroke recovery. We will review tDCS's successful utilization in pilot and proof-of-principle stroke recovery studies, the different modes of tDCS currently in use, and the potential mechanisms underlying the neural effects of tDCS.