Endogenous Intraocular Aspergillus Infection Associated With Systemic Vasculitis.

We report the systemic, ocular, and investigational findings of a 51-year-old male patient with large-vessel vasculitis and presumed ocular Aspergillus infection. He presented with persistent fever with left-sided weakness of the upper and lower limb for the past 15 days accompanied by profound visual loss in the left eye. A neurological examination revealed a left-sided ataxic hemiparesis with a significant reduction of power in both upper and lower limbs with dysarthria. He underwent neuroimaging which revealed a fresh non-hemorrhagic infarct in the left thalamocapsular and left parieto-occipital regions, suggestive of a stroke. A positron emission tomography/computed tomography scan revealed a diffuse low-grade uptake (standardized uptake value = 3.6) associated with a circumferential wall thickening involving the ascending aorta, arch of the aorta, and descending and abdominal aorta, suggestive of active large-vessel vasculitis. On examination, his visual acuity was 6/9 unaided in the right eye and perception of light with inaccurate projection in the left. A dilated fundus examination revealed multiple hemorrhages, cotton-wool spots, and areas of retinal thickening associated with a hard exudate in the right eye. A similar picture was seen in the left eye with the additional findings of a large (1 DD x 1 DD) subretinal whitish-yellowish mass with surrounding superficial retinal hemorrhages in the superior quadrant. A B-scan through the subretinal revealed non-visualization of the retinal pigment epithelium-Bruchs membrane layer with a large subretinal mass with a basal hyporeflective area and hyperreflective areas superiorly, suggesting a choroidal Aspergillus infection with infiltration of the overlying retina but without vitreous seeding. He was treated with anti-epileptics, oral and injectable blood thinners, oral antihypertensives, and oral antidiabetic medication. Intravenous methylprednisolone 1 g once daily was administered for five days, followed by oral prednisolone in tapering doses. In view of the ocular findings and the presumed diagnosis of ocular aspergillus, oral voriconazole 400 mg daily was added. At the last follow-up, the subretinal mass had completely resolved with a residual area of pigmentary degeneration with loss of retinal layer differentiation on the B-scan. There was also a marked reduction in the hemorrhages and cotton-wool spots in either eye, suggesting a marked improvement of the retinal vasculitis. A larger dataset would be needed to confirm a potential causative role for systemic fungal infections in large-vessel vasculitis.

Atypical Optic Neuritis: The Potential Red Flags.

Background: Many potential causes of optic nerve inflammation exist, including typical and atypical causes, which require different management strategies. Objective: The objective of this study is to identify red flags that help differentiate typical from atypical optic neuritis (ON). Materials and Methods: This prospective study included 66 patients (100 eyes) with immune-mediated ON from January 2016 to June 2019, carefully excluding the nonimmune causes. The clinico-radiological features, investigations, therapy, and outcome were analyzed. Results: We evaluated 33 cases each of typical and atypical ON. The typical group included 29 idiopathic ON and four associated with multiple sclerosis. Atypical ON included 19 neuromyelitis optica (NMO), seven MOG-associated ON (MOG-ON), and others due to Sjogren's syndrome, granulomatous polyangiitis, sarcoidosis, and IgG4 disease. Atypical ON occurred significantly and more frequently with extremes of ages (<10 or >70 years), bilateral simultaneous or severe vision loss with early disc pallor, multiple attacks, symptoms/neuro-imaging indicating non-MS disease e.g., long segment ON/myelitis, large confluent lesions, the involvement of optic tract, chiasma, area postrema or diencephalon, and (pachy) meningitis. Systemic involvement and poor outcomes despite steroids and second-line immunosuppression were observed more often in the atypical ON. Conclusions: The red flags indicating atypical ON are onset at extremes of age, multiple attacks, bilateral simultaneous or severe to very severe vision loss, early disc pallor, neurological symptoms, or imaging abnormalities suggesting non-MS disease, systemic involvement, and poor steroid responsiveness. The awareness might help the clinician promptly identify and escalate therapy to ensure a better outcome.

Acute haemorrhagic leukoencephalitis (AHLE) - our experience and a short review.

BACKGROUND: Acute haemorrhagic leukoencephalitis (AHLE), a rare variant of acute disseminated encephalomyelitis (ADEM), often presents differently from classical ADEM, thereby posing a diagnostic challenge to the clinician. AIM: To report AHLE, its clinic-radiological manifestations, process of diagnosis and prognosis. METHOD AND RESULTS: Eight patients presented with altered sensorium, acute focal deficits with or without seizures. Initial workup showed evidence of haemorrhagic lobar or thalamic lesions in seven patients. All patients underwent extensive evaluation for collagen vascular disease and vasculitis profile, autoimmune encephalitis panel and aquaporin-4 antibody, which were found to be normal. Cerebrospinal fluid (CSF) biochemistry and microscopy was non-contributory and CSF viral PCRs, toxoplasma antibodies, cryptococcal antigen were also negative. All patients had progressively worsening sensorium and neurological deficits. Repeat MRIs showed increase in oedema in the lesions and appearance/expansion of haemorrhage in the thalamic/hemispherical lesions. All patients received intravenous methylprednisolone (IVMP) without any benefit. Four patients underwent plasmapheresis (PLEX), one received intravenous immunoglobulin (IVIG) and one received both second line immunotherapies, without significant improvement. Brain biopsy (performed in three patients) showed inflammatory demyelination and areas of haemorrhage, thus confirming the diagnosis. Six patients succumbed in 7-30 days of the illness, despite aggressive treatment and only two survived, albeit with a significant disability. CONCLUSION: AHLE is a rare, yet very severe variant of ADEM. MRI shows lesions with haemorrhages, oedema and mass effect and histology findings reveal inflammatory infiltrates, haemorrhagic foci and fibrinoid necrosis of vessel walls. Prognosis is worse as compared to the classic ADEM, with a high mortality rate. To the best of our knowledge, this is one of the largest series of AHLE to have been reported anywhere in the world. KEYMESSAGE: Acute encephalopathy, multifocal deficits accompanied by haemorrhagic CNS demyelinating lesions with oedema and mass effect are the key features of AHLE. It is a rare, yet very severe form of ADEM with very high morbidity and mortality.

Myelin Oligodendrocyte Glycoprotein (MOG) Antibody-Associated CNS Demyelination: Clinical Spectrum and Comparison with Aquaporin-4 Antibody Positive Neuromyelitis Optica Spectrum Disorder.

BACKGROUND: The clinical phenotypes of myelin oligodendrocyte glycoprotein (MOG) antibody disease, its disease course, and treatment are poorly understood and much work needs to be done towards this. OBJECTIVE: To characterize the clinico-radiologic spectrum and treatment outcomes of MOG antibody disease and differentiate it from aquaporin-4 (AQP-4) antibody positive neuromyelitis optica spectrum disorders (NMO-SD). METHODS: A single-center, observational study from Western India during 2017-2019, of 48 patients with either MOG antibody positive (21 patients) or AQP-4 antibody positive (27 patients) central nervous system demyelination. RESULTS: MOG antibody group had median age 32.2 years, no gender bias, median disease duration 40 months, relapses in 9 patients (43%), and median 2.5 (1-16) episodes per patient. Onset phenotypes included isolated bilateral optic neuritis (ON) (43%), isolated unilateral ON (19%), acute brainstem syndrome (19%), simultaneous ON with myelitis (9%), isolated myelitis (5%), and acute disseminated encephalomyelitis optic neuritis (ADEM-ON) (5%). Characteristic neuroimaging abnormalities were anterior segment longitudinally extensive ON, upper brainstem, and thoracic cord involvement (both short and long segment lesions). Most patients (86%) responded well to steroids, only 3/21 required rescue immunotherapy. In total, 6 out of 46 eyes affected developed permanent visual disability, while one patient had motor disability. The features differentiating MOG from AQP-4 antibody group were: no female predilection, preferential optic nerve involvement, characteristic neuroimaging abnormalities, and favorable therapeutic response and outcome. CONCLUSIONS: MOG disease commonly presents as severe ON, myelitis, acute brainstem syndrome, ADEM or their combinations. Early identification, treatment, and maintenance immunosuppression are necessary. It can easily be differentiated from NMO-SD using clinico-radiological features and therapeutic response.

Does the Tempo and Pattern of Neurological Syndrome Help Diagnose Paraneoplastic Etiology?

BACKGROUND: Paraneoplastic neurological syndromes (PNS) are defined as remote effects of cancer that are not caused by the tumor and its metastasis, or by infection, ischemia or metabolic disruptions. In most patients, the neurological disorder is the manifesting condition and cancer is not detectable clinically at that time. Hence, most often it will be upon the neurologist and not the oncologist to detect paraneoplastic syndrome. AIMS AND OBJECTIVES: To identify characteristic features of a neurological syndrome (presentation pattern and tempo of illness- onset, duration, progression and response to treatment) which indicate a paraneoplastic etiology. MATERIALS AND METHODS: This is a retrospective study. Medical records of all patients who were discharged/ died in Neurology unit of a tertiary care center over a study period of two years with a diagnosis of Paraneoplastic neurological syndrome as per the diagnostic criteria given by F Graus et al1 were studied. RESULTS: Seven PNS cases were identified of which, five had peripheral and two had central nervous system syndrome consistent with the anatomical localisation. Painful pure motor quadriparesis was present in three cases. Subacute onset and rapid progression was seen in six out of seven patients. Ill sustained response to corticosteroid treatment was seen in three patients whereas the remaining four showed no response. In five patients, tumour was detected after the diagnosis of neurological syndrome, as against one patient which had an antecedent tumour and the remaining one patient had classical onconeural antibody without evidence of any detectable tumor. Average time to tumor diagnosis from neurological symptom was 3.5 months. CONCLUSION: A subacute onset, rapidly progressive painful, pure motor quadriparesis; Ganglionopathy in elderly and autoimmune encephalitis with ill sustained or no response to corticosteroids merits consideration of paraneoplastic etiology.

Myotonic Dystrophy Type 1 Clinical, Electrophysiological and Molecular Characterization: Experience at Tertiary Care Centre.

OBJECTIVE: Myotonic dystrophy type 1 (DM1) is the most common myotonic disorder. Molecular genetic testing of the Dystrophia Myotonica-Protein Kinase DMPK gene to detect expansion of CTG repeats is confirmatory. TP-PCR (Triplet Primed-Polymerase Chain Reaction) is rapid and effective screening for the CTG repeat expansions in myotonic dystrophy. Indian data regarding clinical and genetic evaluation of DM1 are sparse. MATERIAL AND METHODS: This was a prospective observational study at a tertiary neurology centre. It included subjects having clinical and electrophysiological evidence of myotonia with CTG repeat expansion of DMPK gene demonstrated by TP-PCR. Diagnostic molecular assessment was done by two-step procedure; conventional PCR and Fragment length analysis followed by TP-PCR. RESULTS: Seventeen patients fulfilled the inclusion criteria. There were fifteen males and two females, with age ranging from 19 to 53 years (mean age 33years). In the phenotype, large calves were seen in three patients and ophthalmoparesis and scapular winging were seen in one patient each. Screening of patients by PCR-Fragment analysis identified all 17 cases to be of DM1. Further confirmatory test by TP-PCR also successfully identified the cases to be of DM1. TP-PCR technique using forward combination primers was used successfully in detecting expansion of CTG repeats in 13 cases whereas in remaining 4 cases reverse primer combination was used successfully. CONCLUSIONS: This series establishes that a combination of PCR- Fragment analysis and TP-PCR is simple and cost effective in determining the diagnosis of Myotonic dystrophy type 1. This study also documents a new clinical observation of calf hypertrophy in genetically confirmed patients with DM1.

Is pushing the wall, the best known method for scapular winging, really the best? A Comparative analysis of various methods in neuromuscular disorders.

INTRODUCTION: 'Pushing the wall' has found acceptance in medical teachings. Other methods of scapular winging are less known. Comparative evaluation of the five available methods has not been undertaken. This study focuses on evaluation of the available methods in groups of neuromuscular disorders to select the most sensitive method and to characterize patterns of scapular winging. A survey of methods practiced by clinicians also forms a part of the study. MATERIALS AND METHODS: Prospective study. Part A: questionnaire based survey of clinicians to explore the preferred method of examination for scapular winging. Part B: comparative analysis of five methods of scapular winging in four categories of neuromuscular disorders [facioscapulohumeral muscular dystrophy (FSHD), limb girdle muscular dystrophy, dystrophinopathies and neurogenic disorders]. RESULTS AND CONCLUSIONS: Forward lowering of arms was the most sensitive method [100%]. The use of this method in clinical teachings and routine bedside examination should be promoted. Pushing the wall was the most popular method, but was fourth in the sensitivity [60.41%]. Arm maneuvers can bring out winging, when it is not apparent at rest. FSHD patients had a unique combination of winging at rest, persistence of winging throughout the range of motion and elevation of scapulae.

A practical approach to enlargement of nerves, plexuses and roots.

Detecting enlargement of accessible nerves is very helpful in assessing patients with peripheral nerve disorders, as only a few types of neuropathy lead to nerve thickening. The three leading causes are leprosy, hereditary motor and sensory neuropathies (types 1 and 3) and chronic inflammatory demyelinating neuropathies. MRI, neurography and ultrasonography allow assessment of clinically inaccessible portions of deep-seated nerves, plexuses and roots. As a result, isolated proximal segment thickenings, as found in chronic inflammatory sensory polyradiculopathy, can now be better evaluated and managed. Similarly, focal nerve enlargements due to infection, inflammation, infiltration and neoplasm are being identified and treated effectively. We present a practical approach to the diagnosis and management of patients with enlarged peripheral nerves, plexuses and roots, including cranial nerves.