Neurological Long-term Sequelae Research Articles

Child and Adolescent Psychiatric Late Effects of Early Herpes Simplex Virus Type 1 Encephalitis

The most common late sequelae of herpes simplex virus type 1 encephalitis (HSVE) include secondary epilepsy, learning, language and memory disorders, and chronic headaches. The typical pattern of HSVE leads to necrosis in the temporal and frontal lobes, thus affecting areas of the brain specifically responsible for the coordination of memory and emotion. This case report describes the course of a patient who, in addition to the typical neurological long-term sequelae, also showed severe psychiatric abnormalities and subsequently addresses the question of why there have been hardly any reports of child and adolescent psychiatric late sequelae after HSVE to date. It can be assumed that the frequency of psychiatric late sequelae is underestimated in pediatrics and in child and adolescent psychiatry and that a targeted anamnestic diagnosis is therefore too often omitted later in child and adolescent psychiatry when psychiatric symptoms appear with a long latency. The second part of the article reviews the state of research to date, revealing that there are too few data on how often and to what extent early-experienced HSVE leads to psychiatric late effects. On the basis of the case report, the specific symptoms to which particular attention should be paid and the brain structures that are typically involved in relation to a psychiatric disorder are presented. From this, it can be deduced, according to the conclusion in the third part of the article, which medications might help. Because of the typical symptomatology of emotional instability some years after HSVE, it is suggested to consider the possibility of mood-stabilizing therapy. The results from the case report presented suggest this.

Meningitis, meningoencephalitis and encephalitis in Bern: an observational study of 258 patients

BackgroundDepending on geographic location, causes of encephalitis, meningoencephalitis and meningitis vary substantially. We aimed to identify the most frequent causes, clinical presentation and long-term outcome of encephalitis, meningoencephalitis and meningitis cases treated in the Inselspital University Hospital Bern, Switzerland.MethodsIn this monocentric, observational study, we performed a retrospective review of clinical patient records for all patients treated within a 3-year period. Patients were contacted for a telephone follow-up interview and to fill out questionnaires, especially related to disturbances of sleep and wakefulness.ResultsWe included 258 patients with the following conditions: encephalitis (18%), nonbacterial meningoencephalitis (42%), nonbacterial meningitis (27%) and bacterial meningoencephalitis/meningitis (13%). Herpes simplex virus (HSV) was the most common cause of encephalitis (18%); tick-borne encephalitis virus (TBEV) was the most common cause of nonbacterial meningoencephalitis (46%), enterovirus was the most common cause of nonbacterial meningitis (21%) and Streptococcus pneumoniae was the most common cause of bacterial meningoencephalitis/meningitis (49%). Overall, 35% patients remained without a known cause. After a median time of 16 months, 162 patients participated in the follow-up interview; 56% reported suffering from neurological long-term sequelae such as fatigue and/or excessive daytime sleepiness (34%), cognitive impairment and memory deficits (22%), headache (14%) and epileptic seizures (11%).ConclusionsIn the Bern region, Switzerland, TBEV was the overall most frequently detected infectious cause, with a clinical manifestation of meningoencephalitis in the majority of cases. Long-term neurological sequelae, most importantly cognitive impairment, fatigue and headache, were frequently self-reported not only in encephalitis and meningoencephalitis survivors but also in viral meningitis survivors up to 40 months after acute infection.

Effects of Poly(ADP-Ribose) Polymerase-1 Inhibition in a Neonatal Rodent Model of Hypoxic-Ischemic Injury.

Background Hypoxia ischemia (HI) to the developing brain occurs in 1–6 in 1000 live births. Large numbers of survivors have neurological long-term sequelae. However, mechanisms of recovery after HI are not understood and preventive measures or clinical treatments are not effective. Poly(ADP-ribose) polymerase-1 is overactivated in response to ischemia. In neonatal mice HI activates PARP-1 but its role in perinatal brain injury remains uncertain. Objective Aim of this study was to explore the effect of TES448 (PARP-1-inhibitor) and hypothermia after an ischemic insult. Design and Methods 10-day-old Wistar rats underwent HI. TES448 was given 10 min, 3 hrs, and 6 hrs after hypoxia. Hypothermia was started 30 min after HI and brains were dissected at P12. Western blotting and histological staining were used to evaluate for degree of injury. Results Protein expression of PARP-1 levels was diminished after TES448 treatment. Cresyl violet and TUNEL staining revealed decreased injury in male rat pups following TES448 and combined treatment. Female rats showed increased numbers of TUNEL-positive cells after combined therapy. TES448 inhibited microglia activation after hypoxic-ischemic injury. A cellular response including NeuN, Olig2, and MBP was not affected by PARP-1-inhibition. Conclusions Inhibition of PARP-1 and hypothermia lead to an alteration of injury but this effect is sexually dimorphic.

Neonatal Transient Idiopathic Hyperinsulinism: Case Report

We report the case of a transient hypoglycemia secondary to idiopathic intermittent hyperinsulinism in a two-day-old newborn. The diagnosis was evoked on clinical data, intermittent hyperinsulinemia, endocrine screening and magnetic resonance imaging MRI brain and pancreatic normal. Neonatal hyperinsulinism intermittent transient idiopathic is a rare cause of neonatal hypoglycemia. Inappropriate secretion of insulin is responsible for unexplained severe hypoglycemia. An early treatment reduces the risk of neurological long-term sequelae.

Patterns of Local and Systemic Cytokines in Bacterial Meningitis and its Relation with Severity and Long-Term Sequelae.

Bacterial meningitis (BM) is a pyogenic infection present in the subarachnoid space, potentially fatal and frequently associated with neurological sequelae. During BM, cytokines (CTs) are locally produced. We sought to determine the CTs’ clinical role as disease severity predictors in adults, which is not completely clear. Using a bead-based flow cytometric assay, levels of six CTs were determined in cerebrospinal fluid (CSF) and plasma from 18 adult BM patients and 19 uninfected controls. Long-term neurological sequelae were evaluated using the Glasgow Outcome Scale (GOS). All evaluated CTs were higher in CSF than in plasma, and the levels of CSF interleukin (IL)-6, IL-8, IL-10, IL-1β, and tumor necrosis factor-α and plasma IL-10 and IL-12p70 were significantly higher in patients with severe sepsis than with sepsis, suggesting an association with clinical severity. There was a strong negative correlation between CSF IL-6 and plasma IL-12p70 with GOS score, supporting the possible role of these CTs in the development of neurological long-term sequelae. These findings could be helpful to identify candidates to receive neuroprotective treatments and early physiotherapy schemes.

31. Intraoperative neurophysiological monitoring for lesions in infratentorial surgery with particular emphasis on long tract functions

During the surgical removal of infratentorial lesions intraoperative neuromonitoring is mostly focused on cranial nerves and brainstem auditory potentials. Despite the known risk of perforating vessel injury during microdissection within the vicinity of the brainstem, there are few reports about intraoperative neuromonitoring with somatosensory (SEP) and motor (MEP) evoked potentials assessing the medial lemniscus and corticospinal tract. This study analyses the occurrence of intraoperative changes in MEP and SEP with regard to lesion location and postoperative neurological outcome. 210 patients (49 ± 13 years, 109 female) undergoing surgeries within the vicinity of the cerebello-pontine angle (77), cerebellum (59), brainstem (40), skull base tumours (26) and others (5) were analysed. 171/210 (81.4%) surgeries were uneventful for long-tract monitoring. 9/39 SEP and MEP-alterations (23%) were transient and without neurological long-term sequelae. Permanent deterioration was seen in 19/39 patients (49%), of which 4 were related to tumour dissection and followed by slight permanent neurological deficit. 11 patients (28%) encountered losses of at least one modality, which were related to surgical microdissection within the vicinity of the brainstem in 9 patients. 4/9 patients suffered a severe long-term deficit. Overall, positive predictive value for long tract neuromonitoring was 0.394, negative predictive value 0.994, sensitivity 0.934 and specificity 0.886. 28/39 (71%) SEP- and MEP-alterations occurred in 66 brainstem respective skull base tumours compared to 11/39 (29%) alterations in all other 144 locations. Tumour location and alterations in intraoperative neuromonitoring significantly correlated with patient outcome (p < 0.001, chi-square test). In summary, long tract monitoring with SEPs and MEPs in infratentorial surgeries has a high sensitivity and negative predictive value indicating postoperative neurological status. It is recommended especially in those surgeries where microdissection within the vicinity of the brainstem might lead to injury of perforating vessels and subsequent perfusion deficit within the brainstem.

Fieberkrämpfe

Febrile seizures are the most common neurological condition in childhood leading to an acute presentation to a pediatrician or consultation in an emergency department. The risk of a febrile seizure is estimated to be approximately 2–5 % in children 6–60 months of age. In the majority of cases the seizures are self-limiting and cease without medical intervention. The disorder is age limited and does not lead to neurological long-term sequelae but a small proportion of patients require a thorough neurological diagnostic evaluation. A comprehensive counseling of the parents is mandatory in children with febrile seizures.

Adjunctive N -Acetyl- l -Cysteine in Treatment of Murine Pneumococcal Meningitis

Despite antibiotic therapy, acute and long-term complications are still frequent in pneumococcal meningitis. One important trigger of these complications is oxidative stress, and adjunctive antioxidant treatment with N-acetyl-l-cysteine was suggested to be protective in experimental pneumococcal meningitis. However, studies of effects on neurological long-term sequelae are limited. Here, we investigated the impact of adjunctive N-acetyl-l-cysteine on long-term neurological deficits in a mouse model of meningitis. C57BL/6 mice were intracisternally infected with Streptococcus pneumoniae. Eighteen hours after infection, mice were treated with a combination of ceftriaxone and placebo or ceftriaxone and N-acetyl-l-cysteine, respectively. Two weeks after infection, neurologic deficits were assessed using a clinical score, an open field test (explorative activity), a t-maze test (memory function), and auditory brain stem responses (hearing loss). Furthermore, cochlear histomorphological correlates of hearing loss were assessed. Adjunctive N-acetyl-l-cysteine reduced hearing loss after pneumococcal meningitis, but the effect was minor. There was no significant benefit of adjunctive N-acetyl-l-cysteine treatment in regard to other long-term complications of pneumococcal meningitis. Cochlear morphological correlates of meningitis-associated hearing loss were not reduced by adjunctive N-acetyl-l-cysteine. In conclusion, adjunctive therapy with N-acetyl-l-cysteine at a dosage of 300 mg/kg of body weight intraperitoneally for 4 days reduced hearing loss but not other neurologic deficits after pneumococcal meningitis in mice. These results make a clinical therapeutic benefit of N-acetyl-l-cysteine in the treatment of patients with pneumococcal meningitis questionable.

Hygromas after endoscopic third ventriculostomy in the first year of life: incidence, management and outcome in a series of 34 patients

Overdrainage in shunted patients is a known predisposing factor for the formation of hygromas, but little is known about risk factors in endoscopic third ventriculocisternostomy (ETV). We retrospectively analysed data of 34 patients younger than 1 year with obstructive hydrocephalus, undergoing ETV, with respect to incidence, management, outcome and possible risk factors for the formation of hygromas. Hygromas were arbitrarily defined as a collection of cerebrospinal fluid of more than 10 mm in diameter over the paramedian hemispheric convexities, diagnosed by ultrasonography. They occurred in 9 of 34 (26%) patients 3 to 28 days after ETV. They were on the operated side in four and bi-lateral in five cases. There was no relevant age difference between patients with hygromas (median 127 days) and those without hygromas (median 166 days). Etiology of obstructive hydrocephalus had no impact on the frequency of hygromas. Hygromas occurred somewhat less frequently when a paediatric endoscope with an outer diameter of 3 mm was used for ETV instead of an endoscope with a diameter of 6 mm. Hygromas were asymptomatic and conservatively managed in five cases; 4 of 34 (12%) patients underwent surgery because of clinical symptoms of increasing intracranial pressure or increasing hygroma diameter. Two patients were treated with a temporary external drainage only and another two patients with an external drainage first and eventually a subduro-peritoneal shunt. There were no neurological long-term sequelae. Clear predisposing factors for the formation of hygromas could not be identified, but the outer diameter of the endoscope may play a role.

The Long-Term Outcome of Infantile Apparent Life-Threatening Event (ALTE): A Follow-Up Study until Midpuberty

The neurological long-term sequelae of an idiopathic apparent life-threatening event (ALTE) were studied in 14 ALTE cases and 12 controls (of similar sex, age, and maturation of puberty). One ALTE case had developed motor and severe learning disabilities. Four other cases and one control were judged as MND (minor neurological deficits). Touwen's neurological profile was less optimal in children with an ALTE history than in controls (p < 0.05). A high amount of associated movements were found in combination with an inability of certain gross motor functions, such as standing or hopping on one leg for sufficiently long or walking on tip-toes or on heels. Fine and gross motor performance tested with the Bruininks-Oseretsky test and behaviour judged with Connors' Rating Scales--Revised, were not different between ALTE cases and controls. Our study provides evidence of neurological long-term sequelae of ALTE.

2-19-06 Neurological long-term sequelae of deep diving

2-19-06 Neurological long-term sequelae of deep diving