Robot-assisted stereotactic brainstem biopsy in children: prospective cohort study.

Tumours located within the brainstem comprise approximately a tenth of all paediatric brain tumours. Surgical biopsy of these tumours is technically challenging and has historically been associated with considerable risk. To this end, robot-assisted surgery theoretically allows for increased accuracy and precision. In this study we report our experience using the Neuromate robot (Renishaw, Gloucestershire, UK) to perform robot-assisted stereotactic biopsy in children with tumours located within the brainstem. An uncontrolled prospective cohort study was performed (phase II) according to the IDEAL model for safe surgical innovation. All cases were recorded on a prospectively maintained database. The database was searched over a 2-year period between the 1st December 2015 and the 31st November 2017 to identify all children with brainstem tumours that underwent robot-assisted stereotactic brain biopsy. When accessible, the post-operative MRI scans and pre-operative plans were compared to assess the target point localisation error (TPLE). Adverse events were recorded prospectively according to whether they resulted in increased hospital stay, caused neurological injury, or lead to death. In all, 11 consecutive children were identified with brain tumours located within the brainstem. In 10/11 cases specimens were diagnostic; in the remaining case a further biopsy was successful. The most frequent pathology was DIPG (7/15). Seven patients underwent an early post-operative volumetric MRI; the calculated median TPLE was 2.7 mm (range 0.5-4.2 mm). There were no surgical complications noted. Robot-assisted stereotactic biopsy in children appears to be feasible and safe. Research databases and comparative studies are warranted to further assess the technique.

A life-threatening brainstem compression by cerebral Echinococcus granulosus.

Cystic echinococcosis (CE) is a zoonotic disease caused by Echinococcus granulosus. It is of worldwide importance, and is widespread in the Mediterranean region and Middle East. This tapeworm shows great intraspecific variation in relation to host specificity, epidemiology and morphology. This variability led in previous years to the identification of ten (G1-G10) different genotypes of the parasite. Cerebral localization of E. granulosus is not common: it especially affects children and is more frequently located in the supratentorial region. It can be life-threatening due to its localization in eloquent areas especially in the posterior fossa. Despite the benign nature of hydatid cyst, invasion of critical areas may cause significant mortality and morbidity in some patients. Urgent surgical decompression and adjuvant medical treatment must be employed as soon as possible in these patients. We present a clinical case of life-threatening brainstem compression in a child due to a rare form of CE which was confirmed with biomolecular techniques. She presented with respiratory distress and progressive quadriparesis. All cysts were removed by microsurgical technique and albendazole was given postoperatively for one year with regular follow-ups.

Fatal infection in two Icelandic stallions caused by Halicephalobus gingivalis (Nematoda: Rhabditida).

Opportunistic infections with the free living nematode Halicephalobus gingivalis are infrequently reported in horses but the cases are widespread geographically. The nematodes are believed to penetrate wounds and subsequently reproduce within the host tissues. This paper reports two cases of a fatal disease in stallions of the Icelandic breed in Iceland. Case 1: a stallion, which sustained injuries to the mouth after an accident, developed severe neurological signs and had to be euthanatized. Histological examination revealed mild inflammation and malacia in the cerebellum associated with the presence of numerous H. gingivalis nematodes. Case 2: a stallion that started swerving to one side and lost balance was euthanatized due to lack of response to therapy and rapid deterioration. Histological examination revealed numerous H. gingivalis nematodes in the cerebellum, brain stem, cervical spinal cord and in the meninges, with minimal reactive changes. In case 1 the infection presumably was acquired by nematodes from soil penetrating through wounds in the mouth. The mode of the H. gingivalis infection in case 2 is uncertain. These are the first cases of H. gingivalis infection reported from Iceland and the second report from the Nordic countries.

Toxoplasma granuloma of brainstem: a rare case.

Toxoplasmosis is a common opportunistic infection in patients with AIDS in whom it frequently presents as intracranial space-occupying lesions. In the immunocompetent patient the most common manifestation is as asymptomatic cervical lymphadenopathy which may be associated with vague systemic manifestations such as fever or myalgia. In very rare cases people with normal immunity may present with meningoencephalitis polymyositis or myocarditis. It is very rare to encounter a brainstem granuloma due to toxoplasma infection in such patients. We report a non-immunocompromised man who presented with multiple cranial nerve palsies due to a brainstem lesion, which turned out to be a toxoplasma granuloma. He recovered completely after a four-week course of Pyrimethamine and Sulphadoxine. An extensive search of the literature failed to reveal any prior reports of a similar nature. This case is being reported because of its rarity and the complete recovery made by the patient.

Fatal subacute necrotising brainstem encephalitis in a young man due to a rare parasitic (Balamuthia) infection.

We describe a case of brainstem inflammation in a young man which at first defied diagnosis. However, after his death, and notwithstanding our inability to find a cause at autopsy, we did not give up. After sending paraffin blocks to the Centers for Disease Control in Atlanta, Georgia, USA, they suggested the diagnosis of Balamuthia (amoebic) infection.

Muscarinic receptors and alpha2-adrenoceptors interact to modulate the respiratory rhythm in mouse neonates.

The respiratory rhythm generator (RRG) is modulated by several endogenous substances, including acetylcholine (ACh) and noradrenaline (NA) that interact in several modulatory processes. To know whether ACh and NA interacted to modulate the RRG activity, we used medullary "en bloc" and slice preparations from neonatal mice where the RRG has been shown to receive a facilitatory modulation from A1/C1 neurons, via a continuous release of endogenous NA and activation of alpha2 adrenoceptors. Applying ACh at 25 microM activated the RRG but ACh had no effects at 50 microM. Applying the ACh receptor agonists nicotine and muscarine facilitated and depressed the RRG, respectively. After yohimbine pre-treatment that blocked the alpha2 facilitation, the nicotinic facilitation was not altered, the muscarinic depression was reversed and ACh 50 microM significantly facilitated the RRG. After L-tyrosine pre-treatment that potentiated the alpha2 facilitation, the muscarinic depression was enhanced. Thus, ACh regulates the RRG activity via nicotinic and muscarinic receptors, the muscarinic receptors interacting with alpha2 adrenoceptors.

Exposure of rat optic nerves to nitric oxide causes protein S-nitrosation and myelin decompaction.

This study investigates the effect of nitric oxide (NO) on both the chemical modifications of CNS proteins and the architecture of the myelinated internode. Incubation of rat optic nerves for 2 h with 1 mM concentration of the NO-donors S-nitroso-N-acetyl-penicillamine (SNAP), ethyl-2-[hydroxyimino]-5-nitro-3-hexeneamide (NOR-3), and 4-phenyl-3-furoxan carbonitrile (PFC) led to decompaction of myelin at the level of the intraperiod line (IPL). In contrast, incubation with 1 mM sodium nitroprusside, which slowly releases NO, sodium nitrite, and N-nitrosopyrrolidine failed to cause myelin disassembly. This suggests that free NO and/or some of its direct oxidation products (e.g., N2O3) are the active molecular species. NO-induced alterations in myelin architecture could not be assigned to protein or lipid degradation, lipid peroxidation, ATP depletion, calcium uptake, protein nitration, protein carbonylation, and nerve depolarization. NO-treatment, however, resulted in the S-nitrosation of a number of proteins. In myelin, one of the major S-nitrosated substrates was identified as proteolipid protein (PLP), an abundant cysteine-rich protein that is responsible for IPL stabilization. Peripheral nervous system myelin, whose stability depends on proteins other than PLP, was not decompacted upon incubation of sciatic nerves with SNAP. It is proposed that NO-mediated nitrosation of sulfhydryl groups is likely to interfere with the normal function of PLP and other important CNS myelin proteins leading to the structural demise of this membrane. These findings are relevant to multiple sclerosis and other inflammatory demyelinating disorders where both excessive NO production and myelin instability are known to occur.

Cysticercosis of cerebellopontine cistern: differential diagnosis using MRI.

We report an example of subarachnoid neurocysticercosis located in the left cerebellopontine cistern of a 60 year-old man. The negative results of the serum and cerebrospinal fluid tests for parasites and the unusual MRI findings, such as the uncommon shape, location and extension pattern, made differential diagnosis difficult. Neurocysticercosis was confirmed by surgical and histopathological findings. The clinical and radiographic features of neurocysticercosis are highly variable. In an endemic area, neurocysticercosis should be considered in the differential diagnosis.

[A case of cerebral coenurosis]. / Su di un caso di cenurosi cerebrale.

In this article the authors describe a case of cerebral coenurosis, a rare infection caused by the larval stage of the tapeworm Taenia multiceps, encountered during their professional practice. The specific epidemiological elements, linked to the parasitic lifecycle in dogs, will also be covered. The authors consider the diagnostic, pathologic and clinical elements that allow differential diagnosis with respect to neurocysticercosis, a parasitic infection caused by the larval form of other Cestoda, discussing possible medical therapeutic approaches (albendazole or praziquantel) and neurosurgical intervention. They emphasize the need to obtain a correct hystopathological diagnosis in order to achieve a differential diagnosis versus the other larval parasitosis. According to current public health regulations this diagnosis must be reported to the Health Official to allow the necessary epidemiological interventions to be planned.

Cellular stress and injury responses in the brains of adult Vietnamese patients with fatal Plasmodium falciparum malaria.

Immunohistochemical techniques have been used to investigate specific patterns of potentially reversible cellular injury, DNA damage, and apoptosis in the brainstems of Vietnamese patients who died of severe Plasmodium falciparum malaria. The degree and pattern of neuronal and glial stress responses were compared between patients with cerebral and non-cerebral malaria (CM), and appropriate non-malaria infected controls. The following markers were examined: (i) heat shock protein 70 (HSP70), for reversible injury; (ii) heme oxygenase-1, for oxidative stress; (iii & iv) two DNA-repair proteins, poly(ADP) ribose polymerase (PARP) and DNA-dependent protein kinase catalytic subunit; (v) poly(ADP) ribose, an end-product of PARP activity; and (vi) caspase-3-active, for apoptosis. Stress responses were found in a range of cell types as reflected by the widespread expression of HSP70. Oxidative stress predominated in the vicinity of vessels and haemorrhages. Some degree of DNA damage was found in the majority of malaria patients, but the distribution and frequency of the damage was much less than that observed in controls with irreversible neuronal injury. Similarly, caspase-3-active expression, as a measure of apoptosis, was no higher in the majority of malaria patients than the negative control cases, although 40% of CM cases expressed caspase-3-active in a small number of neurones of the pontine nuclei or within swollen axons of the pontocerebellar and corticospinal tracts. In conclusion, cells within the brainstem of all patients who died from severe malaria showed staining patterns indicative of considerable stress response and reversible neuronal injury. There was no evidence for a specific pattern of widespread irreversible cell damage in those patients with cerebral malaria.

Solitary cysticercus granuloma of the brainstem. Report of four cases.

Isolated brainstem involvement in patients who have neurocysticercosis is rare. The authors describe the clinical and radiological features of four patients with a solitary cysticercus granuloma of the brainstem and discuss their case management. In three of the patients the onset of symptoms was fairly rapid, occurring over a few days. The granuloma appeared as an enhancing lesion measuring 20 mm or less, with a ring- or disklike appearance on computerized tomography and magnetic resonance imaging. A stereotactic biopsy provided the definitive diagnosis in one patient. In two patients the granuloma resolved spontaneously with complete regression of symptoms and signs and in one patient the granuloma resolved following albendazole therapy. In all patients, outcome was excellent or good (follow-up evaluation 6 months-3 years) with only one patient having persistent paresthesias on one side of his body. Because spontaneous resolution is the rule, a conservative approach to case management, including observation, is recommended. The importance of recognizing this entity and avoiding unnecessary surgical intervention or empirical antituberculous chemotherapy is emphasized.

Clinical study of cerebral malaria in African children.

Of 51 consecutive children with cerebral malaria, fever, convulsions, and drowsiness were the commonest presenting symptoms. Decerebrate and decorticate postures and absent cornea reflex were the commonest brain stem signs. Opening lumbar cerebrospinal (CSF) pressure was raised in all but one of 24 children in whom it was reliably measured [mean 15.2 +/- 5.7 mmHg, range 6-24]. Hyponatraemia occurred in 17 (33%). Acute renal failure was not uncommon; the combination of hypercreatininaemia (plasma creatinine > 100 mumol/L) and hyperkalaemia (plasma potassium > 6.0 mumol/L) was fatal in 5 out of 7 patients in whom it occurred. Disturbances of acid-base status were present in all 40 children in whom it was assessed on admission. Mortality rate was 16% (8 patients). Neurological deficits occurred in 7 (14%) of the survivors and included cortical blindness [3], aphasia [3], hypertonia [3], hearing loss [2], and dystonia [1]. In addition to the present measures aimed at reducing morbidity and morality in children with cerebral malaria, efforts should be directed at rapid assessment of renal function and prompt correction of such dysfunction if found.

Experimental induction of equine protozoal myeloencephalitis in horses using Sarcocystis sp. sporocysts from the opossum (Didelphis virginiana).

Sarcocystis sp. sporocysts isolated from eight feral opossums (Didelphis virginiana) were pooled and fed to 18 commercially reared budgerigars (Melopsittacus undulatus), 14 wild-caught sparrows (Passer domesticus), one wild-caught slate-colored Junco (Junco hyemalis) and five weanling horses (Equus caballus). All budgerigars died within 5 weeks post inoculation (wpi). Histologic examination revealed meronts within the pulmonary epithelia and typical Sarcocystis falcatula sarcocysts developing in the leg muscles. Sparrows were euthanized 13 and 17 wpi and their carcasses were fed to four laboratory raised opossums. Sporocysts were detected in the feces of two opossums on 15 days post inoculation (dpi) and in a third opossum on 40 dpi. Fecal samples from the fourth opossum remained negative; however, sporocysts were found in intestinal digests from all four opossums. Sporocysts were not found in feces or intestinal digest of an additional opossum that was fed three uninoculated sparrows. Five foals were fed sporocysts (Foals 2, 3, 4, 5, and 7) and two foals were maintained as uninoculated controls (Foals 1 and 6). Sporocysts from two additional feral opossums also were fed to foals. Foal 5 was given 0.05 mg kg-1 dexamethasone sodium phosphate daily beginning 2 days before inoculation for a total of 2 weeks. Horse sera were tested three times per week, and cerebrospinal fluid (CSF) samples were tested biweekly for anti-Sarcocystis neurona antibodies by Western blot analysis. No foals had any S. neurona-specific antibodies by Western blot analysis prior to sporocysts ingestion. Seroconversion occurred in Foals 3, 5, and 7 by 24 dpi, followed by positive CSF tests on 28 dpi. Foals 2 and 4 seroconverted by 40 dpi. Cerebrospinal fluid from Foal 2 tested positive by 42 dpi, but Foal 4 remained seronegative throughout the study. Sera and CSF from control Foals 1 and 6 remained seronegative. All foals with positive CSF developed neurologic clinical signs. Neurologic disease was evident in Foals 2 and 3 by 42 dpi and in Foal 7 by 28 dpi. The severity of clinical signs progressed to marked spasticity, hypermetria and ataxia in Foal 7 by the end of the trial. Necropsy examination of inoculated foals did not reveal gross lesions; however, microscopic lesions consistent with equine protozoal myeloencephalitis (EPM) were found in Foals 2, 3, and 7. Protozoa were not observed in the tissue sections. Microscopic lesions consistent with EPM were not found in Foals 4 and 5 or in uninoculated control Foals 1 and 6. Foal 5 had unilateral non-inflammatory lesions in the cervical and thoracic spinal cord consistent with cord compression. These data indicate that the opossum is a definitive host of S. neurona.

Canine neosporosis: a case report and literature review.

A three-year-old, intact female vizsla presented for signs of an acute-onset, progressive spinal cord disease. Postmortem examination revealed multifocal central nervous system (CNS) lesions, severe pneumonia with pulmonary edema, and congestion of the liver. Protozoal cysts were found in multiple spinal cord and brain stem sections. Immunohistochemical staining positively identified these cysts as Neospora caninum. A literature review of Neospora caninum infection in the dog with summary of the pathogenesis, clinical signs, diagnostic evaluation, treatment success, and pathology is presented to provide the clinician with an overview of this increasingly prevalent disease.

Infectious lesions of the brain stem.

Infectious lesions of the brain stem are rare and include primarily abscess and encephalitis. The most common etiologic agents for abscess formation are Streptococcus sp., Staphylococcus sp., and M. tuberculosis. Encephalitis is associated most often with L. monocytogenes and herpes simplex virus infection. Classical brain stem syndromes are uncommon with brain stem infections, and CSF obstruction can be seen with neurocysticercosis. The diagnosis of these lesions has been greatly aided by CT and MR imaging. Microsurgery and stereotaxis are both appropriate techniques for the treatment of brain stem abscess that establish a diagnosis, identify the causative agent, and relieve mass effect on important neural structures. Symptoms of hydrocephalus should be treated with temporary or permanent CSF diversion. Viral involvement of the brain stem is usually self-limited, and improved antimicrobial therapy has contributed to a decrease in the morbidity and mortality of bacterial and parasitic infections. Although once believed to be uniformly fatal, infections of the brain stem have now been successfully treated for more than a decade.