White matter integrity after cannabidiol administration for treatment resistant epilepsy.

OBJECTIVE: The effects of individual cannabinoids on white matter integrity are unclear. Human studies have shown white matter maturation alterations in regular recreational cannabis users with the magnitude of these effects dependent on the age of exposure. However, studies have yet to determine which phytocannabinoids are most responsible for these changes. In the current study, we analyzed the effects of pharmaceutical grade cannabidiol oral solution (CBD; Epidiolex® in the U.S.; Epidyolex® in the EU; 100 mg/mL oral solution) on white matter integrity using diffusion MRI in patients with treatment resistant epilepsy (TRE). METHODS: 15 patients with TRE underwent 3 T diffusion MRI prior to receiving CBD and then again approximately 12 weeks later while on a stable dose of CBD for at least two weeks. DTI analyzes were conducted using DSI Studio and tract-based spatial statistics (TBSS). RESULTS: DTI analysis using DSI Studio showed significant increases in fractional anisotropy (FA) in the right medial lemniscus (p = 0.03), right superior cerebellar peduncle (p = 0.03) and the pontine crossing tract (p = 0.04); decreased mean diffusivity (MD) in the left uncinate fasciculus (p = 0.02) and the middle cerebellar peduncle (p = 0.04); decreased axial diffusivity (AD) in the left superior cerebellar peduncle (p = 0.05), right anterior limb of the internal capsule (p = 0.03), and right posterior limb of the internal capsule (p = 0.02); and decreased radial diffusivity (RD) in the middle cerebellar peduncle (p = 0.03) and left uncinate fasiculus (p = 0.01). The follow-up ANCOVA also yielded significant results when controlling for covariates of CBD dosage, age, sex, change in seizure frequency, and scanner type: FA increased in the pontine crossing tract (p = 0.03); RD decreased in the middle cerebellar peduncle (p = 0.04) and left uncinate fasciculus (p = 0.04). Subsequent TBSS analysis controlling for the same variables yielded no significant white matter differences between groups. CONCLUSION: These findings indicate relatively minor short-term effects of highly-purified plant-derived CBD on white matter structural integrity in patients with TRE.

The effect of medial temporal lobe epilepsy on visual memory encoding.

Effective visual memory encoding, a function important for everyday functioning, relies on episodic and semantic memory processes. In patients with medial temporal lobe epilepsy (MTLE), memory deficits are common as the structures typically involved in seizure generation are also involved in acquisition, maintenance, and retrieval of episodic memories. In this study, we used group independent component analysis (GICA) combined with Granger causality analysis to investigate the neuronal networks involved in visual memory encoding during a complex fMRI scene-encoding task in patients with left MTLE (LMTLE; N=28) and in patients with right MTLE (RMTLE; N=18). Additionally, we built models of memory encoding in LMTLE and RMTLE and compared them with a model of healthy memory encoding (Nenert et al., 2014). For those with LMTLE, we identified and retained for further analyses and model generation 7 ICA task-related components that were attributed to four different networks: the frontal and posterior components of the DMN, visual network, auditory-insular network, and an "other" network. For those with RMTLE, ICA produced 9 task-related components that were attributed to the somatosensory and cerebellar networks in addition to the same networks as in patients with LMTLE. Granger causality analysis revealed group differences in causality relations within the visual memory network and MTLE-related deviations from normal network function. Our results demonstrate differences in the networks for visual memory encoding between those with LMTLE and those with RMTLE. Consistent with previous studies, the organization of memory encoding is dependent on laterality of seizure focus and may be mediated by functional reorganization in chronic epilepsy. These differences may underlie the observed differences in memory abilities between patients with LMTLE and patients with RMTLE and highlight the modulating effects of epilepsy on the network for memory encoding.

Age at stroke determines post-stroke language lateralization.

PURPOSE: To determine how age at the time of left middle cerebral artery stroke affects language lateralization in a combined sample of subjects with perinatal, childhood, and adult stroke. METHODS: 19 participants who had perinatal stroke (<1 month of age), 32 with later stroke, and 51 sex-/age-matched healthy controls (HCs) received fMRI of language using verb generation task (VGT). RESULTS: Percent lesion volumes were not different between groups (perinatal vs. late stroke) when taking brain volume into account (p = 0.084). Perinatal stroke group showed bilateral signal increases compared to more left-lateralized signals in matched HCs; late stroke group and HCs both showed left-hemispheric signal increases. LIs in the stroke groups were consistently more bilateral than in HCs (all p < 0.008) except for the late group's posterior LI (p = 0.080). There was greater proportion of leftward language lateralization in HCs compared to their respective stroke groups (78.9% vs. 31.6% in perinatal; 87.5% vs. 59.4% in late stroke; p = 0.004) and a larger proportion of leftward lateralization in late compared to perinatal stroke (p = 0.039). The age of stroke occurrence showed significant positive associations with global and frontal LI (both p ≤ 0.007). CONCLUSION: As expected, the age of stroke occurrence affects subsequent verb generation lateralization. Greater cortical plasticity is observed in earlier stroke while later stroke is associated with reliance on the repair of the previously damaged left-hemispheric networks.

Sonographic harmonic grey scale imaging of brain perfusion: scope of a new method demonstrated in selected cases.

AIM: Transient response harmonic transcranial sonography is a new bed-side technique which provides information on brain tissue perfusion. This paper demonstrates the scope of perfusion transcranial sonography (p-TCS). METHODS: P-TCS was performed in an axial insonation plane through the thalamus and third ventricle in a case with Moyamoya disease and a patient with bilateral thalamic oedema due to thrombosis of the internal cerebral veins, and compared to results in 10 healthy controls. Signal increase induced by a bolus of an echo-contrast agent (Optison trade mark ) was quantified in regions of interest (ROI) in the thalamus (TH), lentiform nucleus (LN) and the cerebral white matter (WM). RESULTS: In Moyamoya disease p-TCS could demonstrate a decreased perfusion in the WM and LN as a result of bilateral, high-grade stenoses of the intracranial part of the internal carotid artery. Peak intensity was increased in the TH due to collateral cross-over flow from the vertebrobasilar system. TH perfusion was decreased in thrombosis of the internal cerebral vein thrombosis with normal LN perfusion. The extention of the thalamic oedema into the white matter could also be demonstrated by decreased perfusion in the adjacent WM. ROI ratios of different tissues proved helpful in quantifying the perfusion results. CONCLUSION: P-TCS is a new, promising technique that can supply information on pathological brain tissue perfusion at the patient's bed-side.

[Heart and brain]. / Herz und Hirn.

The heart and the brain are closely related, not only proverbially but also anatomically and pathogenetically. Cerebral circulation begins in the heart, through which a major pathomechanism of stroke is predestined: 20-30% of all cerebral infarctions are cardioembolically related. Both organs are equally affected by atherosclerotic processes. Despite this close relationship, generalizing extrapolations from heart to cerebral infarction are usually not applicable. The occurrence of coronary infarction is almost exclusively due to atherosclerosis with plaque rupture, whereas embolic mechanisms such as in cerebral infarction or microangiopathic processes play almost no role. On the other hand, the brain also influences the cardiovascular system. Thus, infarctions particularly in the region of the right insular cortex can induce cardiac arrhythmia and ECG and blood pressure changes. Additionally, vegetative crises with increased sympathicotonia and increased parasympathicotonia are common clinical observations in severe brain disease. A close relation between the two organs can also be observed in preventive pharmacotherapy. Similar principles, however, stand in contrast to considerations of various clinical risks and values, as can be seen for example in anticoagulation or thrombolysis. In this study, special attention is paid to cardioembolic stroke and preventive medicine aspects of coronary and cerebral vascular disorders. In particular, stress is placed on the discerning of commonalities and various evaluations of test results.

[Stroke treatment with stroke unit and rehabilitation by a team. A model for a staged management]. / Schlaganfallbehandlung mit Stroke Unit und Rehabilitation durch ein Team. Ein Modell für eine stadiengerechte Versorgung.

This is a report of an interdisciplinary approach to diagnosis and treatment of stroke, combining a stroke unit and rehabilitation in one clinic. This series contains unselected patients from a narrow surrounding. Mean age of 559 patients was 68.7 years (median 70 years). 25% of patients had an initial Barthel index of < 30, 20% presented with TIA's and PRIND's. 9% suffered from cerebral hemorrhage. The unbroken chain of care allowed a relative short length of stay in the acute care (9.4 days) without prolonging the rehabilitation phase. The one month mortality was 6.7%, one year mortality 18.3%. Discharge to a nursing home was necessary in 5.4%. Overall more than 90% of our patients have been treated continuously in our clinic. Combining modern diagnostics with early onset rehabilitation seem advantageous.

Persistent GAD 65 antibodies in longstanding IDDM are not associated with residual beta-cell function, neuropathy or HLA-DR status.

Persistent humoral autoimmunity to the enzyme glutamic acid decarboxylase (GAD) has been described in a substantial proportion of patients with insulin-dependent diabetes mellitus (IDDM) of long duration. The source of the stimulus for this autoimmune reactivity is still unknown. Because the GAD 65 isoform is mainly expressed in pancreatic beta-cells and in the nervous system we investigated in the present study of the largest number of well characterized patients with longstanding IDDM (n = 105; median duration: 21 years; range: 10-46 years) the presence of autoantibodies to GAD 65 and their relationship to a residual C-peptide response or peripheral and autonomic neuropathy. Additionally we studied the HLA-DR status relative to GAD 65 antibodies in 86 out of the 105 individuals. One hundred healthy control subjects and 100 recent onset IDDM patients were also studied for GAD 65 antibodies. GAD 65 antibodies were detected in a radioligand-binding-assay with recombinant human GAD 65 and were present in 32% of the long-term diabetic patients, 82% of the recent onset IDDM patients and in 3% of the healthy control subjects. A preserved C-peptide response to i.v. glucagon (Hendriksen criteria) was observed in 23% of the long-term IDDM patients. Autonomic neuropathy and peripheral neuropathy was identified using criteria based on both symptoms and formal testing giving a frequency of 67% vs 79%. The HLA specific DR 4/X was observed in 47% and HLA-DR 3/X in 22% of the long-term IDDM patients. Patients who were heterozygous for DR3/DR4 were found in 23% of the cases. GAD 65 antibodies were significantly less frequent in the long-term IDDM patients compared to recent onset IDDM (p < 0.001), and diabetes duration showed a significant negative correlation with GAD 65 antibody index levels (r = 0.22, p < 0.01). Interestingly, GAD 65 antibodies were not significantly correlated either with residual beta-cell function or neuropathy and no particular HLA-DR status was associated with persistent GAD 65 antibodies. In conclusion neither residual beta-cell function nor diabetic neuropathy or a certain HLA-DR specificity are exclusively associated with persistent autoimmunity directed to GAD 65 in longstanding IDDM. The stimulus for the persistent humoral immune response and its significance for the disease process and its complications remain to be established.