A Phase 1 study of GDC-0134, a dual leucine zipper kinase inhibitor, in ALS.

Objective: Dual leucine zipper kinase (DLK), which regulates the c-Jun N-terminal kinase pathway involved in axon degeneration and apoptosis following neuronal injury, is a potential therapeutic target in amyotrophic lateral sclerosis (ALS). This first-in-human study investigated safety, tolerability, and pharmacokinetics (PK) of oral GDC-0134, a small-molecule DLK inhibitor. Plasma neurofilament light chain (NFL) levels were explored in GDC-0134-treated ALS patients and DLK conditional knockout (cKO) mice.

Individualizing Therapy in CIDP: A Mini-Review Comparing the Pharmacokinetics of Ig With SCIg and IVIg.

Immunoglobulin (Ig) therapy is a first-line treatment for CIDP, which can be administered intravenously (IVIg) or subcutaneously (SCIg) and is often required long term. The differences between these modes of administration and how they can affect dosing strategies and treatment optimization need to be understood. In general, the efficacy of IVIg and SCIg appear comparable in CIDP, but SCIg may offer some safety and quality of life advantages to some patients.

Electrical impedance myography correlates with standard measures of ALS severity.

Introduction: Electrical impedance myography (EIM) can be used to assess amyotrophic lateral sclerosis (ALS) progression. The relationship between EIM values and standard assessment measures, however, is unknown.

Methods: EIM 50 kHz phase data from 60 subjects who participated in a longitudinal natural history study of ALS were correlated with handheld dynamometry (HHD), the ALS Functional Rating Scale-Revised (ALSFRS-R) score, and motor unit number estimation (MUNE).

Comprehensive evaluation of corticospinal tract metabolites in amyotrophic lateral sclerosis using whole-brain 1H MR spectroscopy.

Changes in the distribution of the proton magnetic resonance spectroscopy (MRS) observed metabolites N-acetyl aspartate (NAA), total-choline (Cho), and total-creatine (Cre) in the entire intracranial corticospinal tract (CST) including the primary motor cortex were evaluated in patients with amyotrophic lateral sclerosis (ALS). The study included 38 sporadic definite-ALS subjects and 70 age-matched control subjects. All received whole-brain MR imaging and spectroscopic imaging scans at 3T and clinical neurological assessments including percentage maximum forced vital capacity (FVC) and upper motor neuron (UMN) function.

Diffusion tensor imaging of basal ganglia and thalamus in amyotrophic lateral sclerosis.

Purpose: To assess the involvement of basal ganglia and thalamus in patients with amyotrophic lateral sclerosis (ALS) using diffusion tensor imaging (DTI) method.

Methods: Fourteen definite-ALS patients and 12 age-matched controls underwent whole brain DTI on a 3T scanner. Mean-diffusivity (MD) and fractional anisotropy (FA) were obtained bilaterally from the basal ganglia and thalamus in the regions-of-interest (ROIs).

Diffuse large B-cell lymphoma presenting as Miller Fisher syndrome.

We report a patient with diffuse large B-cell lymphoma (DLBCL) who initially presented as Miller Fisher syndrome (MFS) responsive to high-dose immunoglobulin treatment. Detailed investigations for the recurrence of neurological symptoms revealed DLBCL that was responsive to chemotherapy. DLBCL should be considered in the differential diagnosis of patients with MFS who have worsening of their neurological condition after initial improvement with conventional therapy.

1H MRS of basal ganglia and thalamus in amyotrophic lateral sclerosis.

Previous studies have evaluated motor and extramotor cerebral cortical regions in patients with amyotrophic lateral sclerosis (ALS) using (1) H MRS, but none have evaluated the thalamus or basal ganglia. The objective of this exploratory study was to evaluate the subclinical involvement of the basal ganglia and thalamus in patients with ALS using (1) H MRS. Fourteen patients (52±7 years) with sporadic definite ALS and 17 age-matched controls were studied using volumetric MRSI on a 3-T scanner.

Chronic inflammatory demyelinating polyradiculoneuropathy associated with multiple sclerosis.

Objective: To describe temporal profile of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) in patients with definite, relapsing multiple sclerosis (MS).

Background: Peripheral demyelinating neuropathy has been rarely reported in association with central nervous system demyelinating disorder indistinguishable from MS.

Methods: In addition to usual diagnostic studies for CIDP and MS in all 5 patients, we studied proximal segments of nerves using deep tendon reflex latency measurements of biceps reflex, patellar reflex, and ankle reflex.

Chronic inflammatory demyelinating polyradiculoneuropathy in diabetes mellitus.

There is a higher incidence of demyelinating peripheral neuropathy responsive to immunomodulating treatment in patients with diabetes mellitus. The diagnosis is often overlooked and the patients are given the label of "diabetic neuropathy." Progressive symmetric or asymmetric motor deficit, progressive sensory neuropathy in spite of optimal diabetic control, and unusually high cerebrospinal fluid protein level in "diabetic neuropathy" should alert the clinician to the possibility of an underlying treatable demyelinating peripheral neuropathy masquerading as "diabetic neuropathy.

Demyelinating neuropathy in diabetes mellitus.

Background: Recent studies have reported that patients with diabetes mellitus (DM) have a predisposition to develop chronic inflammatory demyelinating polyneuropathy (CIDP).

Objectives: To determine whether patients with DM have a polyneuropathy fulfilling electrophysiologic criteria for CIDP, and whether CIDP is more frequent in patients with type 1 than in patients with type 2 DM.

Methods: We prospectively studied the frequency of electrophysiologic changes meeting the criteria for CIDP in patients with DM seen in our electrophysiology laboratory during a 51-month period (period 1).

Incidence of acute femoral neuropathy following renal transplantation.

Background: Case reports exist of femoral neuropathy following renal transplantation (RTSP) with possible pathophysiology, including direct compression and nerve ischemia. However, the occurrence of acute femoral neuropathy (AFN) following RTSP has not been studied prospectively.

Objective: To determine the occurrence of AFN following RTSP.