99m Technetium-pyrophosphate bone scan: A potential biomarker for the burden of transthyretin amyloidosis in skeletal muscle: A preliminary study.

INTRODUCTION/AIMS: Transthyretin amyloidosis (ATTR) proteins can infiltrate skeletal muscle and infrequently cause a myopathy. 99m Technetium-pyrophosphate (99m Tc-PYP) is a validated biomarker for cardiac involvement in variant and wild-type ATTR (ATTRv and ATTRwt, respectively). The aim of this study was to test the hypothesis that 99m Tc-PYP is a biomarker for muscle burden of ATTR. METHODS: Radioisotope uptake in the deltoid muscles of patients with ATTR was compared to uptake in control subjects without amyloidosis in a retrospective study. 99m Tc-PYP scans were evaluated in 11 patients with ATTR (7 ATTRv, 4 ATTRwt) and 14 control subjects. Mean count (MC) values were measured in circular regions of interest (ROIs) 2.5-3.8 cm2 in area. Tracer uptake was quantified in the heart, contralateral chest (CC), and deltoid muscles. RESULTS: Tracer uptake was significantly higher over the deltoids and heart but not the CC, in patients with ATTR than in control subjects. MC values were 120.1 ± 43.7 (mean ± SD) in ATTR patients and 78.9 ± 20.4 in control subjects over the heart (p = 0.005), 73.3± 21.0 and 63.5 ± 14.4 over CC (p = 0.09), and 37.0 ± 11.7 and 26.0 ± 7.1 averaged over both deltoid muscles (p = 0.014). DISCUSSION: 99m Tc-PYP is a potential biomarker for ATTR amyloid burden in skeletal muscle.

Progressive Multiple Mononeuropathy in a Patient With Familial Transthyretin Amyloidosis After Liver Transplantation.

ABSTRACT: Valine 122 isoleucine (V122I) is the most common mutation associated with familial transthyretin-related amyloidosis (fATTR) in the metropolitan United States. V122I-related fATTR usually presents with cardiomyopathy. When polyneuropathy is encountered, it is usually mild, distal, and axonal in nature. Although liver transplantation improves survival for fATTR neuropathy patients, neuropathy may progress post liver transplantation because of the deposition of wild-type transthyretin. We report a patient with homozygous V122I mutation who presented with asymmetrical, upper limb predominant neuropathy rather early in his disease course, which progressed for a period of 5 years after liver transplantation before stabilization with the initiation of patisiran.

Myasthenia Gravis: Epidemiology, Pathophysiology and Clinical Manifestations.

Myasthenia gravis (MG) is an autoimmune neurological disorder characterized by defective transmission at the neuromuscular junction. The incidence of the disease is 4.1 to 30 cases per million person-years, and the prevalence rate ranges from 150 to 200 cases per million. MG is considered a classic example of antibody-mediated autoimmune disease. Most patients with MG have autoantibodies against the acetylcholine receptors (AChRs). Less commonly identified autoantibodies include those targeted to muscle-specific kinase (MuSK), low-density lipoprotein receptor-related protein 4 (Lrp4), and agrin. These autoantibodies disrupt cholinergic transmission between nerve terminals and muscle fibers by causing downregulation, destruction, functional blocking of AChRs, or disrupting the clustering of AChRs in the postsynaptic membrane. The core clinical manifestation of MG is fatigable muscle weakness, which may affect ocular, bulbar, respiratory and limb muscles. Clinical manifestations vary according to the type of autoantibody, and whether a thymoma is present.

Interictal spike connectivity in human epileptic neocortex.

OBJECTIVE: Interictal spikes are a biomarker of epilepsy, yet their precise roles are poorly understood. Using long-term neocortical recordings from epileptic patients, we investigated the spatial-temporal propagation patterns of interictal spiking. METHODS: Interictal spikes were detected in 10 epileptic patients. Short time direct directed transfer function was used to map the spatial-temporal patterns of interictal spike onset and propagation across different cortical topographies. RESULTS: Each patient had unique interictal spike propagation pattern that was highly consistent across times, regardless of the frequency band. High spiking brain regions were often not spike onset regions. We observed frequent spike propagations to shorter distances and that the central sulcus forms a strong barrier to spike propagation. Spike onset and seizure onset seemed to be distinct networks in most cases. CONCLUSIONS: Patients in epilepsy have distinct and unique network of causal propagation pattern which are very consistent revealing the underlying epileptic network. Although spike are epileptic biomarkers, spike origin and seizure onset seems to be distinct in most cases. SIGNIFICANCE: Understanding patterns of interictal spike propagation could lead to the identification patient-specific epileptic networks amenable to surgical or other treatments.