Desminopathy presenting as late onset bilateral facial weakness, with diagnosis supported by lower limb MRI.

A 63 year old male presented with a 20 year history of facial weakness and several years of nasal regurgitation and dysphonia. Examination revealed bilateral facial weakness with nasal speech. Serum creatine kinase was 918 U/L. Neurophysiological studies suggested a myopathy and biopsy of the left vastus lateralis showed serpentine basophilic inclusions in the sarcoplasm and strong oxidative enzyme activity suggesting mitochondria accumulation. The muscle MRI showed selective fatty replacement within semitendinosus, gastrocnemius and soleus indicative of a desminopathy. A heterozygous missense variant c.17C>G (p.Ser6Trp) was identified within DES, predicted to be pathogenic in silico and previously described in a family with distal limb weakness. There are no previous case reports of desminopathy presenting with facial weakness, to our knowledge. Diagnosis was suggested following myoimaging of clinically unaffected muscles. Our study highlights the importance of muscle MRI in the diagnostic evaluation of muscle disease and further expands the known phenotypic heterogeneity of desminopathies.

Mononeuritis multiplex secondary to Lyme neuroborreliosis.

Lyme neuroborreliosis (LNB) typically presents as a painful radiculitis or a cranial mononeuropathy with lymphocytic meningitis (Bannwarth's syndrome). Isolated peripheral mononeuropathy or multiple mononeuropathy is less frequently recognised. A 58-year-old female with a background of IgA nephropathy and chronic kidney disease presented with a painful left ulnar neuropathy followed within 3 months by superficial radial neuropathy. Initial serum and cerebrospinal fluid (CSF) analysis were unremarkable; nerve conduction study was in keeping with a mononeuritis multiplex. A superficial radial nerve biopsy demonstrated inflammation with axonal injury consistent with a pathologically possible vasculitis. Borrelia antibodies were identified using enzyme-linked immunosorbent assay and immunoblot in serum consistent with active recent Lyme borreliosis. A 6-week course of doxycycline was initiated with gradual resolution of pain and improved power. A repeat nerve conduction study demonstrated improvement in sensory and motor responses. This case report identifies a peripheral nerve syndrome of a mononeuritis multiplex secondary to LNB in the absence of CSF pleocytosis with excellent outcome following antibiotic treatment. Peripheral nervous system manifestations of Lyme borreliosis can mimic a vasculitic neuropathy and therefore should be considered in individuals presenting with a painful mononeuritis multiplex.

Dentatorubral-pallidoluysian Atrophy: An Update.

Background: Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare, autosomal dominantly inherited disorder characterized by myoclonus, epilepsy, ataxia, and dementia. Diagnosis is challenging due to the heterogeneous presentation and symptomatic overlap with other spinocerebellar ataxias. Symptoms vary according to age of onset, with a mean age at onset of 31 years. A CAG repeat expansion in the ATN1 gene results in neuronal intranuclear inclusions, variable neuronal loss, and astrocytosis in the globus pallidus, dentate and red nuclei. No disease-modifying or curative treatments are currently available. Methods: We performed an online literature search using PubMed for all articles published in an English Language format on the topics of DRPLA or ATN1 over the last 10 years. Where these articles cited other research as support for findings, or statements, these articles were also reviewed. Contemporary articles from related research fields (e.g., Huntington's Disease) were also included to support statements. Results: Forty-seven articles were identified, 10 were unobtainable and 10 provided no relevant information. The remaining 27 articles were then used for the review template: seven case reports, seven case series, six model system articles (one review article), four population clinical and genetic studies (one review article), two general review articles, and one human gene expression study. Other cited articles or research from related fields gave a further 42 articles, producing a total of 69 articles cited: 15 case series (including eight family studies), 14 model systems (one review article), 14 population clinical and genetic studies (two review articles), 10 case reports, eight clinical trials/guidelines, four genetic methodology articles, three general review articles, and one human gene expression study. Discussion: DRPLA remains an intractable, progressive, neurodegenerative disorder without effective treatment. Early recognition of the disorder may improve patient understanding, and access to services and treatments. Large-scale studies are lacking, but are required to characterize the full allelic architecture of the disorder in all populations and the heterogeneous phenotypic spectrum, including neuroimaging findings, possible biomarkers, and responses to treatment.