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BACKGROUND Ultrasonography (USG) of the diaphragm is a promising alternative to pulmonary function tests (PFT) for assessing respiratory function in amyotrophic lateral sclerosis/motor neuron disease (ALS/MND). METHODS We studied 33 patients fulfilling Awaji criteria (definite = 14; probable = 12; possible = 7) and 33 age and gender-matched controls. Diaphragm thickness was measured using USG at the end of expiration (DTex) and end of inspiration (DTin). The thickness ratio (TR) was calculated as DTin/DTex. The mean age at onset and duration were 49.73 ± 12.7 years and 13.57 ± 9.7 months, respectively. Men = 25 (75.8%); Limb onset ALS/MND = 24 patients (72.7%); bulbar onset = 9 (27.3%). RESULTS Compared to controls, ALS/MND patients had reduced mean DTex (2.22 ± 0.29 mm vs. 2.02 ± 0.32 mm, p = .012) and DTin (4.0 ± 0.71 mm vs. 3.41 ± 0.38 mm, p

BACKGROUND AND PURPOSE Pathogenic variants in PLEKHG5 have been reported to date to be causative in three unrelated families with autosomal recessive intermediate Charcot-Marie-Tooth disease (CMT) and in one consanguineous family with spinal muscular atrophy (SMA). PLEKHG5 is known to be expressed in the human peripheral nervous system, and previous studies have shown its function in axon terminal autophagy of synaptic vesicles, lending support to its underlying pathogenetic mechanism. Despite this, there is limited knowledge of the clinical and genetic spectrum of disease. METHODS We leverage the diagnostic utility of exome and genome sequencing and describe novel biallelic variants in PLEKHG5 in 13 individuals from nine unrelated families originating from four different countries. We compare our phenotypic and genotypic findings with a comprehensive review of cases previously described in the literature. RESULTS We found that patients presented with variable disease severity at different ages of onset (8-25 years). In our cases, weakness usually started proximally, progressing distally, and can be associated with intermediate slow conduction velocities and minor clinical sensory involvement. We report three novel nonsense and four novel missense pathogenic variants associated with these PLEKHG5-associated neuropathies, which are phenotypically spinal muscular atrophy (SMA) or intermediate Charcot-Marie-Tooth disease. CONCLUSIONS PLEKHG5-associated neuropathies should be considered as an important differential in non-5q SMAs even in the presence of mild sensory impairment and a candidate causative gene for a wide range of hereditary neuropathies. We present this series of cases to further the understanding of the phenotypic and molecular spectrum of PLEKHG5-associated diseases.

Mitochondria regulate the balance between lipid metabolism and storage in the skeletal muscle. Altered lipid transport, metabolism and storage influence the bioenergetics, redox status and insulin signalling, contributing to cardiac and neurological diseases. Lipid storage disorders (LSDs) are neurological disorders which entail intramuscular lipid accumulation and impaired mitochondrial bioenergetics in the skeletal muscle causing progressive myopathy with muscle weakness. However, the mitochondrial changes including molecular events associated with impaired lipid storage have not been completely understood in the human skeletal muscle. We carried out morphological and biochemical analysis of mitochondrial function in muscle biopsies of human subjects with LSDs (n = 7), compared to controls (n = 10). Routine histology, enzyme histochemistry and ultrastructural analysis indicated altered muscle cell morphology and mitochondrial structure. Protein profiling of the muscle mitochondria from LSD samples (n = 5) (vs. control, n = 5) by high-throughput mass spectrometric analysis revealed that impaired metabolic processes could contribute to mitochondrial dysfunction and ensuing myopathy in LSDs. We propose that impaired fatty acid and respiratory metabolism along with increased membrane permeability, elevated lipolysis and altered cristae entail mitochondrial dysfunction in LSDs. Some of these mechanisms were unique to LSD apart from others that were common to dystrophic and inflammatory muscle pathologies. Many differentially regulated mitochondrial proteins in LSD are linked with other human diseases, indicating that mitochondrial protection via targeted drugs could be a treatment modality in LSD and related metabolic diseases. Cover Image for this Issue: doi: 10.1111/jnc.14177.

Purpose: Epilepsy following solitary cerebral cysticercosis(SCC)ispossiblycausedbyperilesionalgliosis,bestvisual-ized on magnetization transfer imaging (MTI).This studyaims to describe development of gliosis around SCC byprospective serial MTI and to correlate this gliosis withlong-termseizureoutcome.Methods: We randomized 123 patients with SCC andnew-onset seizures to treatment with albendazole plusantiepileptics (treatment), or antiepileptics only (con-trol), and performed magnetic resonance imaging (MRI)scans at 0, 3, 6, 12, and 24 months. Prospective follow-up data regarding seizure outcome up to 5 years laterwere collected. MRI studies were analyzed for lesioncharacteristics and perilesional magnetization transfer(MT) hyperintensity.Key Findings: Clinical and radiologic data of 77 patientswere analyzed. Demographic and seizure characteristicswere similar in treatment and control groups. Clinicaldata were available up to 64 months after enrollment. At12 months, 89.5% patients were seizure-free. MTI is moresensitive than routine imaging for detection of perilesion-algliosis.Albendazoletreatmentdidnotaffectimagingorclinical outcome, including development of gliosis. Inde-pendent of duration of follow-up, gliosis was associatedwith more seizures, and with seizure recurrence at12 months; duration of seizures and antiepileptic therapywas longer. Gliosis was not dependent on seizure type orstageofdegenerationatenrollmentorpersistence/calcifi-cationofthelesion.Significance: Perilesional gliosis around SCC helps prog-nosticate seizure outcome. Poorer outcome in patientswith persistent lesions is likely to be related to mecha-nisms other than gliosis. The lack of effect of albendazoleonseizureoutcomemaybeduetoitsinabilitytodecreaseformationofgliosis.KEYWORDS: Solitarycerebralcysticercallesion,Neuro-cysticercosis, Perilesional gliosis, Magnetic resonanceimaging,Magnetizationtransferimaging.