Intrathecal baclofen in hereditary spastic paraparesis: benefits and limitations]

BACKGROUND: Chronic intrathecal delivery of baclofen has been introduced for treatment of severe spinal spasticity. Very little is known about this treatment in hereditary spastic paraparesis. Here we review the benefits and limitations of pump implantation for baclofen delivery in this population. METHODS: Consecutive patients presenting with hereditary spastic paraparesis were assessed for spasticity (Ashworth and Penn scores), muscular strength and walking (speed, comfort and perimeter length). The effect of intrathecal delivery of baclofen was judged after progressive bolus injections or chronic administration by electrical syringe. The pump implantation was proposed when spasticity scores decreased by 2 or more points, with muscular strength preserved and walking area increased. RESULTS: We investigated 6 patients (3 males; mean age 48 years) with hereditary spastic paraparesis. The mean follow-up was 19 years; for 4 patients who received pump implantation, the mean follow-up was 6.2 years. The mean baclofen daily dose was 75 mug. Satisfaction was high for patients who received implantation early instead of waiting for the natural course of the disease. DISCUSSION: Some patients with hereditary spastic paraparesis have good functional improvement with chronic intrathecal delivery of baclofen if walking is still possible. Despite the natural history of the disease, functional results are stable during the first 5 years of treatment. The data indicate a possible compromise between decreased spasticity and muscular strengthening with the treatment.     

Sleep disorders in Parkinson's disease: The contribution of the MPTP non-human primate model

To replicate the sleep–wake disorders of Parkinson's disease (PD) and to understand the temporal relationship between these sleep disturbances and the occurrence of parkinsonism, we performed long-term continuous electroencephalographic monitoring of vigilance states in unrestrained rhesus monkeys using an implanted miniaturized telemetry device and tested the effect of MPTP intoxication on their sleep–wake organization. MPTP injection yielded a dramatic disruption of sleep–wake architecture with reduced sleep efficacy that persisted years after MPTP administration. Primary deregulation of REM sleep and increased daytime sleepiness occurring before the emergence of motor symptoms were a striking feature of the MPTP effect. This was concomitant with a breakdown of dopaminergic homeostasis, as evidenced by decreased dopamine turnover measured after a single MPTP injection. In the long term, partial re-emergence of REM sleep paralleled the partial adaptation to parkinsonism, the latter being known to result from compensatory mechanisms within the dopaminergic system. Altogether, these findings highlight the suitability of the MPTP model of PD as a tool to model the sleep/wake disturbances of the human disease. Ultimately, this may help in deciphering the specific role of dopamine depletion in the occurrence of these disorders.     

New clinicopathological associations and histoprognostic markers in ILAE types of hippocampal sclerosis

Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE‐HS) is a heterogeneous syndrome. Surgery results in seizure freedom for most pharmacoresistant patients, but the epileptic and cognitive prognosis remains variable. The 2013 International League Against Epilepsy (ILAE) histopathological classification of hippocampal sclerosis (HS) has fostered research to understand MTLE‐HS heterogeneity. We investigated the associations between histopathological features (ILAE types, hypertrophic CA4 neurons, granule cell layer alterations, CD34 immunopositive cells) and clinical features (presurgical history, postsurgical outcome) in a monocentric series of 247 MTLE‐HS patients treated by surgery. NeuN, GFAP and CD34 immunostainings and a double independent pathological examination were performed. 186 samples were type 1, 47 type 2, 7 type 3 and 7 samples were gliosis only but no neuronal loss (noHS). In the type 1, hypertrophic CA4 neurons were associated with a worse postsurgical outcome and granule cell layer duplication was associated with generalized seizures and episodes of status epilepticus. In the type 2, granule cell layer duplication was associated with generalized seizures. CD34+ stellate cells were more frequent in the type 2, type 3 and in noHS. These cells had a Nestin and SOX2 positive, immature neural immunophenotype. Patients with nodules of CD34+ cells had more frequent dysmnesic auras. CD34+ stellate cells in scarce pattern were associated with higher ratio of normal MRI and of stereo‐electroencephalographic studies. CD34+ cells were associated with a trend for a better postsurgical outcome. Among CD34+ cases, we proposed a new entity of BRAF V600E positive HS and we described three hippocampal multinodular and vacuolating neuronal tumors. To conclude, our data identified new clinicopathological associations with ILAE types. They showed the prognostic value of CA4 hypertrophic neurons. They highlighted CD34+ stellate cells and BRAF V600E as biomarkers to further decipher MTLE‐HS heterogeneity.     

Understanding Lennox–Gastaut syndrome: insights from focal epilepsy patients with Lennox–Gastaut features

To delineate the clinical and EEG features of adults with focal epilepsy associated with a generalized paroxysmal fast activity (GPFA) pattern on EEG who developed refractory seizures, notably drop attacks, but do not fulfill the classical triad for the diagnosis of Lennox–Gastaut syndrome (LGS) and provide further insight into LGS mechanisms. Among 957 patients admitted to video-EEG monitoring between 2002 and 2015, we retrospectively research adult patients with refractory focal epilepsy, drop attacks and GPFA on EEG. We collected demographic, anamnestic, and clinical data from medical records. We reviewed for all patients the interictal and ictal video-EEG recordings. We identified ten patients with focal epilepsy and electro-clinical features of LGS. As compared to classical LGS patients, our patients: (1) began epilepsy later (15.4 ± 8 years); (2) exhibited exclusively focal onset seizures, including drop attacks seizures linked to focal asymmetrical tonic posturing seizures; (3) had a stable cognition over time and (4) evolved favourably with a good secondary response to treatments in 80% of cases. Interestingly, all patients exhibited apparent diffuse interictal and ictal EEG abnormalities but a detailed analysis revealed that 50% had asymmetrical GPFA and 70% secondary bilateral synchrony processes. We may hypothesize here that a process of “secondary LGS” occurred which produced a worsening of seizures with the apparition of drop attacks and GPFA on EEG. This study brings arguments to consider that some cases of LGS could be linked to the development of a “secondary epileptic network” driven by a primary focal epileptic zone.     

Refractory status epilepticus: Electroconvulsive therapy as a possible therapeutic strategy

Refractory status epilepticus (SE) is a current daily therapeutic challenge. Electroconvulsive therapy (ECT), which is frequently used to treat psychiatric disorders, is known to raise the seizure threshold. As such, ECT could be of major interest in refractory SE. In this paper, we provide a brief overview of ECT in refractory SE. Although no placebo-controlled or open-label study has been published on the efficacy or safety of ECT in refractory SE, eight case reports have been identified. SE cessation was obtained in 80% of cases, and complete recovery was achieved in 27% of patients. Despite the heterogeneity of the ECT parameters used in these articles, we identified some common features that may be recommended for the use of ECT in refractory SE. ECT might be a viable therapeutic strategy for the most resistant and severe cases of SE, particularly after the failure of two inductions of anesthetic coma. This potential indication highlights the urgent need for clinical trials that assess the usefulness of ECT in refractory SE.     

Leber's optic neuropathy associated with disseminated white matter disease: a case report and review

Leber's hereditary optic neuropathy (LHON), a mitochondrial disease, is clinically characterized by a bilateral subacute loss of central vision consecutive to optic nerve involvement. In some cases of LHON, neurological features are reported including multiple sclerosis-like (MSL) phenotype. We report one additional male patient displaying LHON-MSL associated with the prevalent G11778A mutation and review the cases with expendable data published so far in the literature. We discuss the respective roles of inflammation and energetic metabolism dysregulation in the development of brain lesions. We propose to treat these patients early with both antioxidative and immunosuppressive drugs in order to avoid further handicap.