Histological and Clinical Findings in Rabbits Sensitized with GM1 Ganglioside

BACKGROUND: Acute motor axonal neuropathy (AMAN) is a peripheral nerve disorder that attacks motor axons and occurs acutely. AMAN is one type of Guillain–Barre syndrome (GBS) which often attacks men of productive age. Until now, although patients have undergone intravenous immunoglobulin (IVIG) therapy and/or plasmapheresis, long-standing disability remains a problem. In Indonesia, the availability and cost of these therapies are constraints. AIM: Our study aimed to find a proper animal model suitable for AMAN and can be executed in our institution, Naval Health Institute with a hope to find new therapeutic modalities in healing with AMAN. METHODS: GM1 ganglioside immunized in New Zealand male white rabbits with complete Freund’s adjuvant, every 3 weeks until 20 weeks. We evaluated the effects GM1 ganglioside on body weight, functional score, and axon degeneration’s scale. Functional score was examined based on Tarlov’s. Hematoxylin-eosin was used to stain this slide. RESULTS: Rabbits that being immunized with GM1 ganglioside experience a number of neurological signs and symptoms that resemble AMAN, that is, sluggish righting reflex, muscular weakness, flaccid hyper paralysis, and body weight loss. Pathological examination shows extensive degeneration of peripheral nerves, infiltration of macrophages, and perineuritis. CONCLUSION: This histological and clinical findings support that this neuropathy is induced by an autoimmune response delivered by cells that respond to gangliosides.

CIDP and Related Variants and Overlap Disorders

This chapter begins with a history of chronic immunological neuropathies. It then looks in particular at chronic inflammatory demyelinating polyneuropathy (CIDP), which is an immune-mediated peripheral nerve disorder characterized by progressive or relapsing motor or sensory symptoms. It then considers the epidemiology, clinical manifestations, and electrophysiology of CIDP. The chapter examines diagnostic data and diagnostic criteria for CIDP. It then looks at other neuropathies with clinical and electrophysiologic features that are shared with CIDP. Particular attention is given to neuropathy associated with monoclonal gammopathy including IgM associated neuropathy and POEMS syndrome, polyneuropathies associated with specific autoantibodies including antibodies that target nodal and paranodal structures, and multifocal motor neuropathy. For each condition diagnostic data, pathophysiology and treatment are discussed.

Impact of Handedness on Disability After Unilateral Upper-Extremity Peripheral Nerve Disorder

Background: Impairment of the dominant hand should lead to greater disability than impairment of the nondominant hand, but few studies have tested this directly, especially in the domain of upper-extremity peripheral nerve disorder. The aim of this study was to identify the association between hand dominance and standardized measures of disability and health status after upper-extremity peripheral nerve disorder. Methods: An existing database was reanalyzed to identify the relationship between affected-side (dominant vs nondominant) on individuals with unilateral upper-extremity peripheral nerve disorder (N = 400). Primary measure of disability was the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire. Results: We found no differences in standardized measures of disability or health status between patients with affected dominant hand and patients with an affected nondominant hand. However, a post hoc exploratory analysis revealed that patients with an affected dominant hand reported substantially reduced ability to perform 2 activities in the DASH questionnaire: “write” and “turn a key.” Conclusions: Following unilateral upper-extremity peripheral nerve disorder, impairment of the dominant hand (compared with impairment of the nondominant hand) is associated with reduced ability to perform specific activities, but this reduced ability is not reflected in standardized measures of disability and health status. To adequately identify disability following unilateral impairment of the dominant hand with the DASH, individual items must be used instead of the total score. New or alternative measures are also recommended.

Trk receptor signaling and sensory neuron fate are perturbed in human neuropathy caused by Gars mutations

Charcot–Marie–Tooth disease type 2D (CMT2D) is a peripheral nerve disorder caused by dominant, toxic, gain-of-function mutations in the widely expressed, housekeeping gene, GARS. The mechanisms underlying selective nerve pathology in CMT2D remain unresolved, as does the cause of the mild-to-moderate sensory involvement that distinguishes CMT2D from the allelic disorder distal spinal muscular atrophy type V. To elucidate the mechanism responsible for the underlying afferent nerve pathology, we examined the sensory nervous system of CMT2D mice. We show that the equilibrium between functional subtypes of sensory neuron in dorsal root ganglia is distorted by Gars mutations, leading to sensory defects in peripheral tissues and correlating with overall disease severity. CMT2D mice display changes in sensory behavior concordant with the afferent imbalance, which is present at birth and nonprogressive, indicating that sensory neuron identity is prenatally perturbed and that a critical developmental insult is key to the afferent pathology. Through in vitro experiments, mutant, but not wild-type, GlyRS was shown to aberrantly interact with the Trk receptors and cause misactivation of Trk signaling, which is essential for sensory neuron differentiation and development. Together, this work suggests that both neurodevelopmental and neurodegenerative mechanisms contribute to CMT2D pathogenesis, and thus has profound implications for the timing of future therapeutic treatments.

Phase II multi-institutional prospective trial of nab-paclitaxel as second-line chemotherapy for advanced gastric cancer refractory to fluoropyrimidine with modified dose reduction criteria (CCOG1303).

91 Background: Nab-paclitaxel (nab-PTX) is a candidate as second-line chemotherapy for gastric cancer, with the response rate (RR) of 28% and overall survival (OS) of 9.2 months in that setting in Japan (J-0200). Adverse events (AE) of grade 3 or more were frequent and included neutropenia in 49%, leucopenia in 20% and peripheral nerve disorder (PND) in 24%. Modified dose reduction criteria to manipulate the doses earlier might be more practical, given the relative dose intensity (RDI) of paclitaxel (PTX) in the conventional weekly regimen. Phase II prospective trial was conducted to explore the efficacy and safety of nab-PTX with modified dose reduction criteria. Methods: Patients with histologically confirmed metastatic or recurrent gastric adenocarcinoma that progressed during the fluoropyrimidine-containing first-line chemotherapy were eligible. Patients pretreated with PTX were excluded. Nab-PTX (260 mg/m2) was administered triweekly. Dose reduction was regulated according to predefined toxicity criteria which included neutropenia < 1000/mm3 and/or PND with grade 2 or more. Treatment was to be continued until PD, unacceptable toxicity, or patient’s refusal. The primary endpoint was progression free survival (PFS). Secondary endpoints were OS, RR and toxicity. Results: A total of 50 patients were enrolled from 14 institutions, 47 of whom were eligible for efficacy analyses. The median number of treatment given was 4 cycles (range, 1-25). Of total administration throughout the trial of 280 cycles, dose reduction was needed in 52 cycles (22%). The RDI was 80%. The median PFS was 3.5 months (range, 0.4-20.2) that was equivalent to the expected value designed in the study. The median OS was 9.0 months (range, 1.4-22.1) and RR was 16% (95%CI 2-30). AE of grade 3 or more included neutropenia in 49%, leucopenia in 21% and PND in 11%. Febrile neutropenia occurred in 1 patient (2%). The median time to treatment failure was 3.5 months (range, 0.4-18.0). Conclusions: The modified dose reduction criteria for triweekly administration of nab-PTX resulted in decreased incidence of severe PND without fall in efficacy. Clinical trial information: UMIN000012247.

PRESENCE OF TRIPLE GANTZER'S MUSCLE - A RARE ANATOMICAL VARIATION

Anomalous muscles usually do not result in adverse symptoms but are of academic interest. However, these muscles can create neurovascular compression at times. Muscle anomalies of the upper extremity are recognized causes of peripheral nerve disorder. Koloh-Nevin Syndrome (Anterior Interosseous Nerve Syndrome) caused by the compression neuropathy of the anterior interosseous nerve in the forearm is believed to occur because of its compression by the accessory heads of flexor pollics longus (FPLah) and flexor digitorum profundus (FDPah). The above two accessory muscles are also called Gantzer's muscle. During routine cadaveric dissection, we encountered multiple Gantzer's muscles in a 60 year-old- formalin embalmed male cadaver. Along with the usual FPLah and FDPah described by Gantzer, we too observed an accessory muscle in relation to the flexor digitorum superficialis (FDS). All the three anomalous muscles had a common origin from the under cover of the FDS fibers and by fibrous band above the insertion of brachialis. The presence of multiple additional muscles in the forearm flexor compartment is rare and clinically significant.

A Novel Fuzzy Expert System for the Identification of Severity of Carpal Tunnel Syndrome

The diagnosis of carpal tunnel syndrome, a peripheral nerve disorder, at the earliest possible stage is very crucial because if left untreated it may cause permanent nerve damage reducing the chances of successful treatment. Here a novel Fuzzy Expert System designed using MATLAB is proposed for identification of severity of CTS. The data used were the nerve conduction study data obtained from Kannur Medical College, India. It consists of thirteen input fields, which include the clinical values of the diagnostic test and the clinical symptoms, and the output field gives the disease severity. The results obtained match with the expert’s opinion with 98.4% accuracy and high degrees of sensitivity and specificity. Since quantification of the intensity of CTS is a crucial step in the electrodiagnostic procedure and is important for defining prognosis and therapeutic measures, such an expert system can be of immense use in those regions where the service of such specialists may not be readily available. It may also prove useful in combination with other systems in providing diagnostic and predictive medical opinions and can add value if introduced into the routine clinical consultations to arrive at the most accurate medical diagnosis in a timely manner.