Mitochondrial DNA 13513G>A Mutation Causing Leber Hereditary Optic Neuropathy Associated With Adult-Onset Renal Failure.

BACKGROUND: Leber hereditary optic neuropathy (LHON) is one of the more common mitochondrial diseases and is rarely associated with mitochondrial renal disease. We report 3 unrelated patients with a background of adult-onset renal failure who presented to us with LHON and were shown to have a heteroplasmic mitochondrial DNA mutation (m.13513G>A). METHODS: Retrospective chart review. RESULTS: All 3 patients had a background of chronic renal failure and presented to us with bilateral optic neuropathy (sequential in 2) and were found to have heteroplasmic m.13513G>A mutations in the MT-ND5 gene. Two of the patients were females (aged 30 and 45 years) with chronic kidney disease from their 20s, attributed to pre-eclampsia, one of whom also had diabetes and sudden bilateral hearing loss. One patient was a male (aged 54 years) with chronic kidney disease from his 20s attributed to IgA nephropathy. His mother had diabetes and apparently sudden bilateral blindness in her 70s. Renal biopsy findings were variable and included interstitial fibrosis, acute tubular necrosis, focal segmental glomerulosclerosis, and IgA/C3 tubular casts on immunofluorescence. Mild improvements in vision followed treatment with either idebenone or a combination supplement including coenzyme Q10, alpha-lipoic acid, and B vitamins. CONCLUSIONS: Our cases expand the clinical syndromes associated with m.13513G>A to include bilateral optic neuropathy and adult-onset renal disease. This highlights that in patients with bilateral, especially sequential, optic neuropathy a broad approach to mitochondrial testing is more useful than a limited LHON panel. Mitochondrial diseases present a diagnostic challenge because of their clinical and genetic variability.

Invasive Fungal Sinusitis Presenting as Acute Posterior Ischemic Optic Neuropathy.

Invasive fungal sinusitis causes painful orbital apex syndrome with ophthalmoplegia and visual loss; the mechanism is unclear. We report an immunocompromised patient with invasive fungal sinusitis in whom the visual loss was due to posterior ischaemic optic neuropathy, shown on diffusion-weighted MRI, presumably from fungal invasion of small meningeal-based arteries at the orbital apex. After intensive antifungal drugs, orbital exenteration and immune reconstitution, the patient survived, but we were uncertain if the exenteration helped. We suggest that evidence of acute posterior ischaemic optic neuropathy should be a contra-indication to the need for orbital exenteration in invasive fungal sinusitis.

Neuro-ophthalmology of invasive fungal sinusitis: 14 consecutive patients and a review of the literature.

BACKGROUND: Invasive fungal sinusitis is a rare condition that usually occurs in immunocompromised patients and often presents as an orbital apex syndrome. It is frequently misdiagnosed on presentation and is almost always lethal without early treatment. DESIGN: Retrospective case series of 14 consecutive patients with biopsy-proven invasive fungal sinusitis from four tertiary hospitals. PARTICIPANTS: Fourteen patients (10 men and 4 women; age range 46-82 years). METHODS: Retrospective chart review of all patients presenting with invasive fungal sinusitis between 1994 and 2010 at each hospital, with a close analysis of the tempo of the disease to identify any potential window of opportunity for treatment. MAIN OUTCOME MEASURES: Demographic data, background medical history (including predisposing factors), symptoms, signs, radiological findings, histopathological findings, treatment approach and subsequent clinical course were recorded and analysed. RESULTS: Only one patient was correctly diagnosed at presentation. Only two patients were not diabetic or immunocompromised. The tempo was acute in two patients, subacute in nine patients and chronic in three patients. In the subacute and chronic cases, there was about 1 week of opportunity for treatment, from the time there was a complete orbital apex syndrome, and still a chance for saving the patient, to the time there was central nervous system invasion, which was invariably fatal. Only two patients survived - both had orbital exenteration, as well as antifungal drug treatment. CONCLUSIONS: Invasive fungal sinusitis can, rarely, occur in healthy individuals and should be suspected as a possible cause of a progressive orbital apex syndrome.

Wilson Disease: A Case Report of Psychosis Preceding Parkinsonism.

BACKGROUND A first psychotic episode requires the exclusion of toxic-metabolic, inflammatory, infective, and neoplastic causes. Wilson disease is a rare, autosomal recessive disorder of copper metabolism and can present with neuropsychiatric symptoms secondary to copper accumulation in the brain. CASE REPORT We describe the case of a 48-year-old man with parkinsonism on a background of longstanding schizophrenia and psychotic depression in the setting of previously undiagnosed Wilson disease. The common history of neuropsychiatric disturbance and neuroleptic use complicated the assessment of parkinsonism. However, close attention to the temporal appearance of symptoms and signs differentiated his case from drug-induced parkinsonism, which commonly develops hours to weeks after commencement or uptitration of antipsychotic medication. The early features of sialorrhea and dysarthria were also atypical for idiopathic Parkinson disease. The diagnosis was confirmed by serum copper testing and supported by Kayser-Fleischer rings on bedside ophthalmological examination. Magnetic resonance imaging (MRI) of the brain demonstrated copper accumulation in the basal ganglia and pons, contributing to the characteristic neurological manifestations of an akinetic-rigid syndrome with dysarthria. CONCLUSIONS Serum copper testing is easily obtained and should be considered as part of the first-line investigations for new neuropsychiatric disturbances. Although rare, Wilson disease, if diagnosed early, is a potentially treatable and reversible cause of psychosis. With advanced disease, extrapyramidal findings on examination correlate with MRI brain changes, aiding the clinical assessment in differentiating the disease from drug-induced parkinsonism.

A Window Into the Whole Story: Temporal Bone Plasmacytoma Presenting With a Mobile Third Window.

A 63-year-old man presented with imbalance when coughing due to a respiratory tract infection. He had a history of multiple myeloma with a plasmacytoma of the left temporal bone. Examination revealed a positive leftward head impulse test, no spontaneous nystagmus, left-beating positional nystagmus, and left-beating Valsalva-induced nystagmus. Videonystagmography, audiology, and comprehensive vestibular function tests revealed a subtotal left peripheral audio-vestibular loss. Temporal bone computed tomography showed an unchanged bony erosion of the left labyrinth from 2 years prior. Vertigo subsided after treatment of the respiratory tract infection. Although no tumor progression was evident, coughing had triggered a preexisting third mobile window to declare itself. Laryngoscope, 131:E966-E969, 2021.

Retrograde memory after unilateral stroke.

Over the past two decades, there has been a growing interest in understanding the neural underpinnings of memory of the past. Numerous patients with retrograde amnesia after acute brain damage have been described, but often the causative lesions are bilateral and/or fairly diffuse and one question that has arisen is whether a unilateral lesion is sufficient to cause retrograde memory impairment. In addition, the impact of lesion side and site on the material specificity and temporal extent of retrograde memory deficits has remained unclear. We set out to investigate these issues by comparing 20 patients who had recently had a unilateral stroke that involved (but was not necessarily limited to) either the frontal or temporal lobe to a group of 10 matched normal control subjects on tests of memory of events and semantic details from the autobiographical and public domains. Results indicated that a unilateral lesion was sufficient to cause significant retrograde memory impairment, with right-sided lesions affecting recall of autobiographical events more than left-sided lesions. The memory deficits in these patients were most often relatively mild, but temporally pervasive rather than characterised by a traditional temporal gradient. Furthermore, memory of events (both autobiographical and public) was impaired in patients who had had a stroke that included the hippocampus, but not in those whose strokes spared this region. Finding that patients with mesial temporal lesions had difficulty remembering details related to public events, even when offered recognition choices, raises the possibility that part of their memory storage network (and not just their retrieval abilities) was compromised.

Acute unilateral peripheral vestibulopathy in neurosyphilis.

INTRODUCTION: Neurosyphilis producing basal meningitis presenting as sequential transient cranial nerve palsies was well recognized before the antibiotic era. OBJECTIVE: To report two patients presenting with acute unilateral peripheral vestibulopathy due to syphilitic basal meningitis. RESULTS: In Case 1 basal meningitis occurred early in the secondary phase of the infection, in Case 2 in the late latent phase. The diagnosis was not made immediately in either case; in Case 1 after previous presentation with increasing hearing loss and then with facial palsy and then a subsequent presentation with optic neuritis; in Case 2 after investigation for possible lymphoma. CONCLUSION: Syphilitic basal meningitis in either the secondary or in the latent phase can present as acute unilateral peripheral vestibulopathy with transient involvement of the facial or auditory nerve.