Molecular typing of Leptospira spp. in farmed and wild mammals reveals new host-serovar associations in New Zealand.

AIMS: To apply molecular typing to DNA isolated from historical samples to determine Leptospira spp. infecting farmed and wild mammals in New Zealand. MATERIALS AND METHODS: DNA samples used in this study were extracted from urine, serum or kidney samples (or Leptospira spp. cultures isolated from them) collected between 2007 and 2017 from a range of domestic and wildlife mammalian species as part of different research projects at Massey University. Samples were included in the study if they met one of three criteria: samples that tested positive with a lipL32 PCR for pathogenic Leptospira; samples that tested negative by lipL32 PCR but were recorded as positive to PCR for pathogenic Leptospira in the previous studies; or samples that were PCR-negative in all studies but were from animals with positive agglutination titres against serogroup Tarassovi. DNA samples were typed using PCR that targeted either the glmU or gyrB genetic loci. The resulting amplicons were sequenced and typed relative to reference sequences. RESULTS: We identified several associations between mammalian hosts and Leptospira strains/serovars that had not been previously reported in New Zealand. Leptospira borgpetersenii strain Pacifica was found in farmed red deer (Cervus elaphus) samples, L. borgpetersenii serovars Balcanica and Ballum were found in wild red deer samples, Leptospira interrogans serovar Copenhageni was found in stoats (Mustela erminea) and brushtail possums (Trichosurus vulpecula), and L. borgpetersenii was found in a ferret (Mustela putorius furo). Furthermore, we reconfirmed previously described associations including dairy cattle with L. interrogans serovars Copenhageni and Pomona and L. borgpetersenii serovars Ballum, Hardjo type bovis and strain Pacifica, sheep with L. interrogans serovar Pomona and L. borgpetersenii serovar Hardjo type bovis, brushtail possum with L. borgpetersenii serovar Balcanica, farmed deer with L. borgpetersenii serovar Hardjo type bovis and hedgehogs (Erinaceus europaeus) with L. borgpetersenii serovar Ballum. CONCLUSIONS: This study provides an updated summary of host-Leptospira associations in New Zealand and highlights the importance of molecular typing. Furthermore, strain Pacifica, which was first identified as Tarassovi using serological methods in dairy cattle in 2016, has circulated in animal communities since at least 2007 but remained undetected as serology is unable to distinguish the different genotypes. CLINICAL RELEVANCE: To date, leptospirosis in New Zealand has been diagnosed with serological typing, which is deficient in typing all strains in circulation. Molecular methods are necessary to accurately type strains of Leptospira spp. infecting mammals in New Zealand.

Intravenous thrombolysis is unsafe in stroke due to infective endocarditis.

Embolic stroke is the most common neurological complication of infective endocarditis and a major source of morbidity and mortality. Septic embolism is considered a contraindication to intravenous thrombolysis in patients with ischaemic stroke because of concerns over an increased risk of intracranial haemorrhage. We describe a patient with occult endocarditis who was treated with thrombolysis for acute stroke and review other cases reported in the literature.

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.

Limbic encephalitis - a review.

The clinical features of limbic encephalitis are diverse and early diagnosis of the disorder is frequently difficult. Four patients with limbic encephalitis are described. An antineuronal antibody was identified in three of these patients. Antibodies directed against voltage-gated potassium channels, the N-methyl-D-aspartate receptor and an unidentified neuropil antigen were each found in one patient. The fourth patient had multifocal paraneoplastic encephalitis associated with small cell lung cancer. The clinical and imaging findings associated with these antibodies and the other antineuronal antibodies described in patients with limbic encephalitis are reviewed. An approach to the diagnosis and management of limbic encephalitis is presented.

Ethnic differences in syringomyelia in New Zealand.

OBJECTIVE: To determine the prevalence of syringomyelia in a defined population in New Zealand and measure the prevalence of syringomyelia in the three main ethnic groups (Maori, Pacific people and Caucasians/others) living in this region. METHODS: A retrospective study of all confirmed cases of syringomyelia diagnosed in residents of northern New Zealand from 1961 to 2003. RESULTS: In all, syringomyelia was diagnosed in 137 patients. The mean age at onset of symptoms was 27.5 years and mean age at diagnosis was 32.6 years. The incidence of new cases increased from 0.76/100,000 a year between 1962 and 1971 to 4.70/100,000 a year by 1992-2001. The prevalence of syringomyelia in 2003 was 8.2/100,000 people: 5.4/100,000 in Caucasians or others, 15.4/100,000 in Maori and 18.4/100,000 in Pacific people (chi2 = 37.0, p<0.0001). Syringomyelia was more often associated with an isolated Chiari I malformation in Pacific people (84.4%) as compared with 42.9% of Maori and 38.2% of Caucasians or others (chi2 = 62.3, p<0.0001). CONCLUSION: The prevalence of syringomyelia is higher in northern New Zealand than in studies carried out before the advent of magnetic resonance imaging. The prevalence is particularly high in Maori and Pacific people. The cause of the ethnic differences in the prevalence of syringomyelia identified in this study is unexplained and warrants further investigation.

Changing attitudes to the management of ischaemic stroke between 1997 and 2004: a survey of New Zealand physicians.

AIM: In 1997, a survey of New Zealand physicians' opinions on the management of stroke was carried out. Since then, there have been a number of advances in stroke therapy. We have repeated the 1997 survey to assess changes in physicians' opinions on stroke management. METHODS: A questionnaire was sent to 293 physicians responsible for patients admitted with acute stroke to hospitals throughout New Zealand. It included questions on the management of acute stroke and secondary prevention and was based on the 1997 questionnaire. RESULTS: Responses were received from 211 physicians of whom 174 (82%) managed patients with an acute stroke. The number of respondents who thought that stroke units were efficacious has increased (57% in 1997 to 89%, P < 0.001). The use of aspirin acutely (P < 0.001) and intravenous tissue plasminogen activator (P = 0.006) has also increased. In 2004, antihypertensive therapy for secondary stroke prevention would be commenced if the blood pressure was 150/90 by 98% of respondents and 140/90 by 70% of respondents. In 2004, a statin would be commenced if the total cholesterol level was 4.0 mmol/L by 56% of respondents and 5.0 mmol/L by 91% of respondents. CONCLUSIONS: This survey has shown important changes in the management of ischaemic stroke over the past 7 years.

Leptomeningeal infiltration as the presenting manifestation of a malignant glioma.

Infiltration of the leptomeninges by a malignant glioma typically occurs with recurrent supratentorial tumors, but patients may present with leptomeningeal gliomatosis before the primary tumor is diagnosed. This report describes two patients who presented with headache and signs of multifocal neurological disease. One of the patients had neurofibromatosis type I. In both patients the cerebrospinal fluid examination showed a mild pleocytosis, but malignant cells were not detected. The diagnosis of leptomeningeal gliomatosis was not confirmed until autopsy, but in retrospect imaging showed a small, asymptomatic primary tumor in both patients. Leptomeningeal gliomatosis should be considered in the differential diagnosis of chronic meningitis, if the patient is afebrile and if there are multifocal neurological signs, even when a primary tumor is not obvious.

Expression of an antigen in small cell lung carcinoma lines detected by antibodies from patients with paraneoplastic dorsal root ganglionpathy.

We have identified an autoantibody that reacts with a neuronal nucleoprotein in the serum of patients with small cell lung carcinoma (SCLC) and the paraneoplastic syndrome, subacute sensory neuronopathy (SSN). A similar antigen has been found in the tumor from one of these patients. To determine the distribution of this antigen, immunoblots of a homogenate from the SCLC of another patient with SSN, six SCLC cell lines from patients without SSN, five non-SCLC cell lines, and one ovarian carcinoma cell line were reacted with serum from five patients with SCLC and SSN. Control sera were obtained from two patients with SSN without cancer, two patients with SSN associated with tumors other than SCLC, two patients with paraneoplastic cerebellar degeneration, and five patients with SCLC but no SSN. The sera from all five patients with SCLC and SSN identified a Mr 35,000 to 40,000 antigen in neurons, in all of six SCLC cell lines and in the SCLC tumor homogenate. The antigen was not detected in other tumor cell lines. Control sera did not react with these bands, in either neurons or SCLC cell lines. Bound IgG was eluted from the blot of one SCLC cell line after reaction with SSN serum. Eluates from the Mr 35,000 to 40,000 area reacted with neuronal nuclei in the cerebral cortex by an immunoperoxidase technique; eluates from other areas of the blot were negative. These findings support the hypothesis that the autoantibody in SSN arises in reaction to an antigen shared between SCLC and neuronal nuclei.

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.

Is there a temporal pattern in the occurrence of subarachnoid hemorrhage in the southern hemisphere? Pooled data from 3 large, population-based incidence studies in Australasia, 1981 to 1997.

BACKGROUND AND PURPOSE: Publications on the temporal pattern of the occurrence of subarachnoid hemorrhage (SAH) have produced conflicting results. Variations between studies may relate to the relatively small numbers of SAH cases analyzed, including those in meta-analyses. METHODS: We identified all cases of SAH from 3 well-designed population-based studies in Australia (Adelaide, Hobart, and Perth) and New Zealand (Auckland) during 3 periods between 1981 and 1997. The diagnosis of SAH was confirmed with CT, cerebral angiography, cerebrospinal fluid analysis, or autopsy in all cases. Information on the time of occurrence of each event was obtained. Risk ratios (RRs) and 95% CIs were calculated using Poisson regression, with age, sex, smoking status, and history of hypertension entered in the model as covariates. RESULTS: A total of 783 cases of SAH were registered. Age- and sex-adjusted RRs of SAH occurrence were highest in the period between 6 AM and 12 MIDNIGHT (RR 3.2, 95% CI 2.4-4.3) and in winter and spring (RR 1.3, 95% CI 1.1-1.5; RR 1.3, 95% CI 1.1-1.5; respectively). No particular pattern of SAH occurrence was observed according to the day of the week. Restriction of the analyses to proved aneurysmal SAH did not substantially change the point estimates. CONCLUSIONS: Circadian and circaseptan (weekly) fluctuations of SAH occurrence in the southern hemisphere are similar to those in the northern hemisphere, but the occurrence of SAH in Australasia exhibits clear seasonal (winter and spring) peaks.

Opsoclonus, myoclonus, ataxia, and encephalopathy in adults with cancer: a distinct paraneoplastic syndrome.

The clinical and pathological findings in 4 adults with cancer and opsoclonus were compared with those of 15 other patients described elsewhere. The clinical syndrome of paraneoplastic opsoclonus is characterized by the acute onset of opsoclonus and truncal ataxia, often accompanied by encephalopathy, myoclonus and a cerebrospinal fluid pleocytosis. Unlike most other paraneoplastic syndromes, the course is often remitting and relapsing. Neuropathological examination in 3 of our patients showed lymphocytic cuffing of occasional blood vessels throughout the central nervous system, associated with a mild, diffuse proliferation of microglia in 1 patient. Apart from a mild, patchy loss of Purkinje cells in 1 patient, there was no loss of neurons from the cerebellum, brainstem, cerebral hemispheres, or spinal cord. These patients differ from those with the more common paraneoplastic cerebellar degeneration by the predominance of truncal over limb ataxia, the presence of myoclonus, the absence of severe dysarthria, a tendency for remission, and the preservation of Purkinje cells.

Activation of epileptiform activity by mental arithmetic.

Activation of epileptic seizures or electroencephalographic epileptiform discharges by mental calculation is rare. We report the case of a 34-year-old right-handed accountant with a 20-year history of generalized tonoclonic seizures. Although clinical seizures were unrelated to performance of mental arithmetic, epileptiform activity appeared when she attempted difficult mental arithmetic. Apart from one occasion, epileptiform discharges did not impair her ability to provide accurate answers to mathematical problems.

Superficial siderosis of the central nervous system: a late complication of cerebellar tumors.

OBJECTIVE: To describe the clinical and radiologic features of superficial siderosis of the CNS after treatment of a cerebellar tumor. METHODS: Clinical assessment and MRI in four patients with superficial siderosis were performed. RESULTS: Four patients with superficial siderosis had been treated for a primary cerebellar tumor (astrocytoma in three patients, medulloblastoma in one patient) during childhood. All patients were treated with surgery and three received radiotherapy. Slowly progressive bilateral sensorineural hearing loss, gait ataxia, and limb ataxia appeared 8 to 22 years after diagnosis of the cerebellar tumor. Other clinical features were mild cognitive impairment, dysarthria, nystagmus, optic neuropathy, anosmia, and upper motor neuron signs. The CSF contained erythrocytes and increased protein. MRI with fast spin-echo T2-weighted and gradient-echo T2* sequences showed a hypointense rim of iron coating the surface of the cerebellum and brainstem. Twenty-one other patients who had survived more than 5 years after treatment of a primary cerebellar tumor did not have symptoms or signs suggestive of superficial siderosis. CONCLUSIONS: Superficial siderosis is an uncommon late complication of the treatment of a childhood cerebellar tumor, but it is probably underrecognized. The diagnosis should be suspected in patients who present with slowly progressive sensorineural hearing loss and ataxia many years after eradication of a childhood cerebellar tumor.

Sensory neuronopathy and Sjögren's syndrome: clinical and immunologic study of two patients.

In two patients, a sensory neuronopathy was the initial presentation of Sjögren's syndrome. There was no systemic or peripheral nerve vasculitis. Immunochemical studies failed to demonstrate specific antibodies against the nervous system. These features suggest that the damage to the sensory neurons might not be mediated by humoral immune mechanisms.

Autoantibodies in paraneoplastic syndromes associated with small-cell lung cancer.

An antineuronal autoantibody has been identified in serum from 14 patients, 8 women and 6 men, with small-cell lung carcinoma (SCLC) and a neurologic disorder. Neurologic symptoms began prior to diagnosis of the SCLC in 12 patients. The dominant neurologic disorder was a subacute sensory neuronopathy (SSN) in eight patients, SSN plus lower motor neuron weakness (2 patients), SSN plus autonomic neuropathy (1 patient), cerebellar ataxia (1 patient), myelopathy (1 patient), and multifocal nervous system disease (encephalomyelitis) in one patient. The presence of the same autoantibody in patients with SSN, encephalomyelitis, and autonomic neuropathy suggests that these diseases are different manifestations of the same nosologic process. With one exception, treatment of the tumor, immunosuppressive drugs, and plasmapheresis did not influence the course of the neurologic illness. The autoantibody was not identified in sera from more than 400 controls subjects, including patients with SSN associated with other tumors, SSN without malignancy, other paraneoplastic syndromes, and SCLC without neurologic symptoms. The autoantibody is a highly specific marker of the paraneoplastic syndromes associated with SCLC and its detection in a patient not known to have cancer should prompt a careful search for SCLC.

Anterior opercular syndrome, caused by herpes simplex encephalitis.

Bilateral frontal and parietal opercular lesions cause a syndrome characterized by paralysis of the masticatory, facial, pharyngeal, and tongue muscles (the anterior opercular syndrome). The anterior opercular syndrome can occur in patients with herpes simplex encephalitis (HSE), but in most of these patients the diagnosis of HSE was not confirmed. We describe the anterior opercular syndrome in four patients with HSE. In two of these patients, the anterior opercular syndrome dominated the clinical picture, but in the other two patients it was overshadowed by other manifestations of HSE. The diagnosis of HSE was confirmed by detection of herpes simplex virus (HSV) DNA in the CSF (two patients), culture of the HSV from a brain biopsy (one patient), and elevated HSV antibody titers in the CSF (one patient). Our patients made a partial recovery. Acute onset of weakness of masticatory, facial, pharyngeal, and glossal muscles, accompanied by fever, headache, and partial motor seizures of the face should suggest HSE.

Intestinal pseudo-obstruction, myasthenia gravis, and thymoma.

Two patients presented with abdominal pain, recurrent vomiting, weight loss, and constipation secondary to intestinal pseudo-obstruction. Both patients had symptoms and signs of myasthenia gravis, acetylcholine receptor antibodies, and thymoma. In one patient inflammatory cell infiltrates and occasional degenerate neurons were found in the myenteric plexus. The gastrointestinal symptoms resolved during treatment with pyridostigmine. The close temporal relationship between the onset of the gastrointestinal symptoms and the detection of myasthenia gravis and thymoma suggests that intestinal pseudo-obstruction can be a paraneoplastic syndrome associated with thymoma.

A variant of the anti-Purkinje cell antibody in a patient with paraneoplastic cerebellar degeneration.

An anti-Purkinje cell antibody was found in the serum and CSF of a man with adenocarcinoma of the lung and paraneoplastic cerebellar degeneration (PCD). This antibody differed from the autoantibodies found in patients with gynecologic cancer and PCD in that it produced a different pattern of Purkinje cell cytoplasmic staining, did not react with PCD antigens in Purkinje cell Western blots, and the antigen had a different species distribution. Unlike the antinuclear antibody found in patients with PCD and small-cell lung carcinoma, the antigen was restricted to the cytoplasm of Purkinje cells. If autoantibodies are important in the pathogenesis of PCD, this case illustrates that they can recognize different antigenic epitopes in the nervous system, but cause similar clinicopathologic syndromes.

Autoimmune pathogenesis of paraneoplastic neurological syndromes.

"Remote effects" of cancer on the nervous system (paraneoplastic syndromes) are disorders of the nervous system of unknown cause that occur almost exclusively, or with greatly increased frequency, in patients with identifiable or occult cancer. There are several hypotheses concerning the pathogenesis of these rare disorders. One hypothesis is that the underlying tumor and portions of the nervous system share antigens and that an autoimmune response generated against the tumor causes the nervous system disorder. Evidence supporting this hypothesis includes the ability to transmit the Lambert-Eaton Syndrome (a paraneoplastic syndrome involving the neuromuscular junction) to experimental animals by infusing IgG from patients with the disorder, the presence of autoantibodies against Purkinje cell neurons in some patients with paraneoplastic cerebellar degeneration, and the presence of autoantibodies against many neurons in patients with sensory neuronopathy and encephalomyelitis. Other evidence supporting the hypothesis is presented in this review.