Jennifer Pereira

Medically refractory neurosarcoidosis treated with infliximab.

Neurosarcoidosis can worsen despite standard immunosuppressive therapy, a situation for which there is no established medical management. We present three cases of medically refractory neurosarcoidosis treated with infliximab. All three patients showed a clinical response to this treatment and side effects were limited. A summary of reported cases of neurosarcoidosis treated with infliximab is included. This case series supports a role for infliximab in the treatment of patients with medically refractory neurosarcoidosis.

Incidence and prevalence of NMOSD in Australia and New Zealand

Objectives We have undertaken a clinic-based survey of neuromyelitis optica spectrum disorders (NMOSDs) in Australia and New Zealand to establish incidence and prevalence across the region and in populations of differing ancestry. Background NMOSD is a recently defined demyelinating disease of the central nervous system (CNS). The incidence and prevalence of NMOSD in Australia and New Zealand has not been established. Methods Centres managing patients with demyelinating disease of the CNS across Australia and New Zealand reported patients with clinical and laboratory features that were suspicious for NMOSD. Testing for aquaporin 4 antibodies was undertaken in all suspected cases. From this group, cases were identified who fulfilled the 2015 Wingerchuk diagnostic criteria for NMOSD. A capture–recapture methodology was used to estimate incidence and prevalence, based on additional laboratory identified cases. Results NMOSD was confirmed in 81/170 (48%) cases referred. Capture–recapture analysis gave an adjusted incidence estimate of 0.37 (95% CI 0.35 to 0.39) per million per year and a prevalence estimate for NMOSD of 0.70 (95% CI 0.61 to 0.78) per 100 000. NMOSD was three times more common in the Asian population (1.57 (95% CI 1.15 to 1.98) per 100 000) compared with the remainder of the population (0.57 (95% CI 0.50 to 0.65) per 100 000). The latitudinal gradient evident in multiple sclerosis was not seen in NMOSD. Conclusions NMOSD incidence and prevalence in Australia and New Zealand are comparable with figures from other populations of largely European ancestry. We found NMOSD to be more common in the population with Asian ancestry.

C9ORF72 and UBQLN2 mutations are causes of amyotrophic lateral sclerosis in New Zealand: a genetic and pathologic study using banked human brain tissue.

Amyotrophic lateral sclerosis (ALS) is a devastatin g neurodegenerative disease which causes progressive and eventually fatal loss of motor func tio . Here we describe genetic and pathological characterisation of brain tissue banked from 19 ALS patients over nearly 20 years at the Department of Anatomy and the Centre for Brain Research, Unive rs ty of Auckland, New Zealand. We screened for mutations in SOD1, TARDBP, FUS, and C9ORF72 genes, and for neuropathology caused by phosphorylated TDP-43, dipeptide repeats and ubiqui lin. We identified two cases with C9ORF72 repeat expansions. Both harboured phosphorylated TD P-43 and dipeptide repeat inclusions. We show that dipeptide repeat inclusions can incorporate or occur independently of ubiquilin. We also identified one case with a UBQLN2 mutation, which showed phosphorylated TDP-43 and characteristic ubiquilin protein inclusions. This i s the first study of ALS genetics in New Zealand, adding New Zealand to the growing list of countries in which C9ORF72 repeat expansion and UBQLN2 mutations are detected in ALS cases.

Neurological complications of acute multifocal placoid pigment epitheliopathy

Acute multifocal placoid pigment epitheliopathy (AMPPE) is an autoimmune chorioretinal disease that can be complicated by neurological involvement. There is limited information on this potentially treatable condition in the neurological literature. The objective of this patient series is to describe the neurological complications of AMPPE. We retrospectively identified patients with neurological complications of AMPPE seen at Auckland Hospital between 2008 and 2013 and summarised cases in the literature between 1976 and 2013. We identified five patients with neurological complications of AMPPE at Auckland Hospital and 47 reported patients. These patients demonstrated a spectrum of neurological involvement including isolated headache, stroke or transient ischaemic attack, seizures, venous sinus thrombosis, optic neuritis, sensorineural hearing loss and peripheral vestibular disorder. We propose criteria to define AMPPE with neurological complications. A cerebrospinal fluid (CSF) lymphocytosis in a patient with isolated headache may predict the development of cerebrovascular complications of AMPPE. Patients with cerebrovascular complications of AMPPE have a poor prognosis with high rates of death and neurological disability among survivors. Predictors of poor outcome in those who develop neurological complications of AMPPE are a relapsing course, generalised seizures and multifocal infarction on MRI. All patients with neurological complications of AMPPE, including headache alone, should be investigated with an MRI brain and CSF examination. Patients with focal neurological symptoms should receive intravenous (IV) methylprednisolone followed by a tapering course of oral steroids for at least 3months. Patients with AMPPE and an isolated headache with a CSF pleocytosis should be treated with oral steroids.

C9ORF72 and UBQLN2 are genetic causes of ALS in New Zealand: A genetic and pathological study using banked human brain tissue

Amyotrophic lateral sclerosis (ALS) is a devastatin g neurodegenerative disease which causes progressive and eventually fatal loss of motor func tio . Here we describe genetic and pathological characterisation of brain tissue banked from 19 ALS patients over nearly 20 years at the Department of Anatomy and the Centre for Brain Research, Unive rs ty of Auckland, New Zealand. We screened for mutations in SOD1, TARDBP, FUS, and C9ORF72 genes, and for neuropathology caused by phosphorylated TDP-43, dipeptide repeats and ubiqui lin. We identified two cases with C9ORF72 repeat expansions. Both harboured phosphorylated TD P-43 and dipeptide repeat inclusions. We show that dipeptide repeat inclusions can incorporate or occur independently of ubiquilin. We also identified one case with a UBQLN2 mutation, which showed phosphorylated TDP-43 and characteristic ubiquilin protein inclusions. This i s the first study of ALS genetics in New Zealand, adding New Zealand to the growing list of countries in which C9ORF72 repeat expansion and UBQLN2 mutations are detected in ALS cases.

C9ORF72 and UBQLN2 are genetic causes of ALS in New Zealand

Amyotrophic lateral sclerosis (ALS) is a devastatin g neurodegenerative disease which causes progressive and eventually fatal loss of motor func tio . Here we describe genetic and pathological characterisation of brain tissue banked from 19 ALS patients over nearly 20 years at the Department of Anatomy and the Centre for Brain Research, Unive rs ty of Auckland, New Zealand. We screened for mutations in SOD1, TARDBP, FUS, and C9ORF72 genes, and for neuropathology caused by phosphorylated TDP-43, dipeptide repeats and ubiqui lin. We identified two cases with C9ORF72 repeat expansions. Both harboured phosphorylated TD P-43 and dipeptide repeat inclusions. We show that dipeptide repeat inclusions can incorporate or occur independently of ubiquilin. We also identified one case with a UBQLN2 mutation, which showed phosphorylated TDP-43 and characteristic ubiquilin protein inclusions. This i s the first study of ALS genetics in New Zealand, adding New Zealand to the growing list of countries in which C9ORF72 repeat expansion and UBQLN2 mutations are detected in ALS cases.

A pain in the neck

A 75-year-old man presented to the emergency department with dizziness. He had been in good health until 5 weeks before admission, when his ladder slipped while he was cutting branches in a tree. He fell on to his upper back and left shoulder but did not hit his head or lose consciousness. Following the fall, he developed persisting left-sided neck and shoulder pain. A chiropractor manipulated his neck six times without significant relief. On the day of admission, he became non-specifically unwell following his morning walk and went to lie down. On getting up he felt extremely dizzy, both spinning and light-headed. He lay down but remained unwell, with shortness of breath and chest discomfort. The symptoms completely resolved in less than 5 min. He came to the emergency department by ambulance. There was no past history or specific risk factors for vascular disease and he took no regular medications. On examination, his blood pressure was 170/80 mm Hg but other vital signs were normal. The emergency department registrar documented normal cardiovascular, respiratory and abdominal examinations, with no spinal tenderness or neck movement restriction. Neurological examination was normal, including eye movements, coordination and gait. ### Question 1 What investigations would you arrange? The symptoms are non-specific and the differential diagnosis is wide. Routine blood tests can help to exclude dehydration, metabolic disturbances or infection. A 12-lead ECG, cardiac enzymes and a period of cardiac monitoring can help to exclude cardiac ischaemia or an arrhythmia. Although dizziness is non-specific, the lack of improvement with lying down argues against simple presyncope. Further neurological assessment with a Dix–Hallpike manoeuvre and head impulse test might help. The symptoms in isolation probably do not warrant neuroimaging; however, the neck pain following trauma and subsequent chiropractic manipulation raise the possibility of vertebral artery dissection, and the need for MR scan of …

Reply: Treatment of refractory neurosarcoidosis with tumour necrosis factor inhibitors--what lies ahead?

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