cover image European Journal of Neurology

European Journal of Neurology

2014 - Volume 21
Issue 12 | December 2014

Short Communication

Background and purpose

Studies on the impact of infectious diseases affecting the nervous system are sparse.

Methods

All patients with neuroinfectious diseases (NIDs) who were treated at our Department of Neurology from 2005 until 2009 were retrospectively analyzed.

Results

Patients with NIDs required treatment at the intensive care unit in 34.8%. The mortality rate of patients with NIDs was significantly higher than that of other inpatients with neurological diseases (5.1% vs. 3.0%, respectively,  = 0.018).

Conclusion

In summary, this study shows that patients with NIDs are severely ill and mortality is high.

Original Article

Background and purpose

The diagnosis of amyotrophic lateral sclerosis (ALS) relies on identification of a combination of upper and lower motor neuron signs. In order to improve the diagnostic sensitivity for ALS, Awaji criteria were developed, in part to better incorporate neurophysiological measures, although assessment of upper motor neuron dysfunction remained clinically based. Given that cortical hyperexcitability appears to be an early feature in ALS, the present study assessed the diagnostic utility of a threshold tracking transcranial magnetic stimulation technique as an aid to the research‐based Awaji criteria in establishing an earlier diagnosis of ALS.

Methods

Prospective studies were undertaken on a cohort of 82 patients with suspected ALS and results were compared with 34 healthy controls.

Results

Short‐interval intracortical inhibition (SICI) was significantly reduced in ALS patients ( < 0.0001), with a comparable reduction evident in the Awaji groups (SICI 1.3% ± 1.3%; SICI 1.4% ±1.7%). Central motor conduction time was significantly prolonged ( < 0.001), whereas the motor evoked potential amplitude ( < 0.05) and intracortical facilitation ( < 0.05) were increased. The frequency of transcranial magnetic stimulation abnormalities was similar across Awaji subgroups, and addition of transcranial magnetic stimulation abnormalities as a diagnostic category enabled reclassification of 88% of Awaji possible patients to Awaji probable/definite.

Conclusions

Cortical excitability studies potentially facilitate an earlier diagnosis of ALS when combined with clinical and conventional neurophysiological findings, albeit in a research setting.

Editorial

Abstract

Click to view the accompanying paper in this issue.

CME Article

Background and purpose

Morphological brain changes related to hypovitaminosis D have been poorly studied. In particular, the age‐related decrease in vitamin D concentrations may explain the onset of white matter abnormalities (WMA) in older adults. Our objectives were (i) to investigate whether there was an association between serum 25‐hydroxyvitamin D (25OHD) concentration and the grade of WMA in older adults and (ii) to determine whether the location of WMA was associated with 25OHD concentration.

Methods

One hundred and thirty‐three Caucasian older community‐dwellers with no clinical hydrocephalus (mean 71.6 ± 5.6 years; 43.6% female) received a blood test and a magnetic resonance imaging scan of the brain. The grades of total, periventricular and deep WMA were scored using semiquantitative visual rating scales from T2‐weighted fluid‐attenuated inversion recovery images. The association of WMA with as‐measured and deseasonalized 25OHD concentrations was evaluated with the following covariates: age, gender, body mass index, use of anti‐vascular drugs, number of comorbidities, impaired mobility, education level, Mini‐Mental State Examination score, medial temporal lobe atrophy, serum concentrations of calcium, thyroid‐stimulating hormone and vitamin B12, and estimated glomerular filtration rate.

Results

Both as‐measured and deseasonalized serum 25OHD concentrations were found to be inversely associated with the grade of total WMA (adjusted  = −0.32,  = 0.027), specifically with periventricular WMA (adjusted  = −0.15,  = 0.009) but not with deep WMA (adjusted  = −0.12,  = 0.090). Similarly, participants with 25OHD concentration <75 nM had on average a 33% higher grade of periventricular WMA than those with 25OHD ≥75 nM ( = 0.024). No difference in average grade was found for deep WMA ( = 0.949).

Conclusions

Lower serum 25OHD concentration was associated with higher grade of WMA, particularly periventricular WMA. These findings provide a scientific basis for vitamin D replacement trials.

Original Article

Background and purpose

Our aim was to prospectively describe the course of headache during the first year of idiopathic intracranial hypertension (IIH).

Methods

Patients with newly diagnosed IIH were consecutively included from December 2010 to June 2013. Treatment according to standard guidelines was initiated. Headache history was obtained by headache diaries and standardized interviews performed at baseline and after 1, 2, 3 and 12 months. Parallel changes in papilledema were assessed by optical coherence tomography (OCT). All patients had comprehensive neuro‐ophthalmological examinations including automated perimetry.

Results

Forty‐four patients were included. Thirty‐five patients completed the 12‐month follow‐up. Dramatic improvement in headache occurred within the first weeks after diagnosis. After 1 year, 15 patients reported no or only infrequent headache. However, 15 of the remaining 20 patients reported sustained chronic headache. Early age of onset and high diagnostic intracranial pressure (ICP) were associated with better headache outcome (≤1 headache days/month) after a year. Papilledema decreased rapidly within the first 2 months of diagnosis. After 1 year, OCT measures had normalized. Visual outcome was excellent in most patients.

Conclusions

Although headache in 43% of patients responded well to ICP management, sustained long‐term headache was seen in the remaining patients, despite resolution of papilledema. Headache in IIH may thus be attributed to more complex mechanisms than ICP elevation alone. High ICP and young age were associated with better headache outcome. Early treatment according to standard guidelines seems sufficient to ensure excellent visual outcome in the vast majority of patients.

Original Article

Background and purpose

Subcutaneous immunoglobulin (SCIG) is superior to placebo treatment for maintenance of muscle strength during 12 weeks in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). The present study evaluated whether SCIG preserves muscle strength for 1 year in an open‐label follow‐up study.

Methods

Seventeen responders to intravenous immunoglobulin (IVIG) who had participated in the previous study of SCIG versus placebo in CIDP were included. After one IVIG infusion 2 weeks prior to baseline, all continued on SCIG treatment at weekly equal dosage and were evaluated after 3, 6 and 12 months. Primary end‐points were changes in muscle strength evaluated by isokinetic dynamometry in four affected muscle groups and a composite score of muscle performance and function tests, including Medical Research Council (MRC) score, grip strength, 40‐m walking test (40‐MWT) and nine‐hole peg test (9‐HPT). Secondary end‐points were changes of each of the listed parameters at each time point as well as an overall disability sum score (ODSS).

Results

The dose of SCIG was significantly unaltered during the follow‐up period. Overall the isokinetic dynamometry value increased by 7.2% ( = 0.033) and after 3, 6 and 12 months by 5.7%, 8.2% and 6.8% (ns). The overall composite score at all time intervals and for each interval remained unchanged. Amongst the secondary parameters the MRC score increased significantly by 1.7% ( = 0.007), whereas grip strength, 40‐MWT, 9‐HPT and ODSS remained unchanged.

Conclusion

SCIG preserves muscle strength and functional ability in patients with CIDP who previously responded to IVIG. SCIG should be considered as an alternative in long‐term treatment of CIDP patients.

Original Article

Background

The oxaliplatin (ΟΧΑ)‐based regimens FOLFOX and XELOX can cause peripheral neuropathy. It is unknown if ΟΧΑ, alone or in combination regimens, affects the Autonomous Nervous System (ANS). Accordingly, we evaluated the impact of ΟΧΑ‐based chemotherapy on the ANS.

Methods

We enrolled 36 patients with colorectal cancer, treated with adjuvant mFOLFOX6 or XELOX chemotherapy, and 22 healthy volunteers. For the assessment of ANS function, participants completed a questionnaire and underwent neurophysiological examination at three time points (baseline, 3–4 months and 6–8 months after the first chemotherapy cycle). ANS testing included assessment of the adrenergic cardiovascular function (orthostatic hypotension‐OH), parasympathetic heart innervation (ratio 30/15) and Sympathetic Skin Response (SSR).

Results

The values of the 30/15 ratio were significantly reduced at the two time point assessments compared to baseline (Wilcoxon signed ranks test, both <0.001), while patients had more often diastolic OH at the 6–8 month evaluation compared to baseline (=0.039). In contrast, SSR was not affected. The incidence of positive responses in the questionnaire assessing the subjective impact of symptoms attributable to ANS dysfunction was higher at the two time points compared to baseline (=0.036 and =0.020).

Conclusions

Oxaliplatin‐based chemotherapy is associated with significant effects on the adrenergic cardiovascular reaction and the parasympathetic heart innervation, whereas SSR remains untouched.

Original Article

Background and purpose

Alternating hemiplegia of childhood (AHC) is a rare neurological disease characterized by recurrent paroxysmal attacks of hemiplegia. The aim of the study was to assess the recovery cycle of the somatosensory evoked potentials (SEPs) in a group of AHC patients.

Methods

Seven AHC patients and 10 control age‐matched subjects (CS) were recruited. Right and left median nerve SEPs were recorded. The somatosensory system excitability was assessed by calculating the SEP changes after paired electrical stimuli. All patients were studied during the interictal phase, whilst four patients were studied also during the ictal phase.

Results

In AHC patients during the interictal phase, the amplitudes of the cervical N13 and of the cortical N20, P24 and N30 responses showed a faster recovery than in CS. In AHC patients during the ictal phase, the cortical N20 recovery cycle was prolonged compared with the interictal phase.

Conclusions

A shortened SEP recovery cycle in AHC during the interictal phase suggests multilevel somatosensory system hyperexcitability in AHC. A partial recovery of this phenomenon during the ictal phase possibly reflects a functional reset of the somatosensory system. Overall, there is a disinhibition of the somatosensory system in AHC, a functional change of brain function associated with a possible involvement of the Na/K channels. This abnormality and its partial recovery during the attacks might be linked to the pathophysiological and genetic mechanisms of the disease.

Original Article

Background and purpose

Cervical dystonia (CD) patients usually receive repeated botulinum neurotoxin (BoNT) injections. The aims of this study were to evaluate the feasibility of motor endplate zone (MEZ) detection of relevant cervical muscles in CD patients receiving chronic BoNT treatment and to compare the treatment effect of half‐dosed, endplate‐targeted injections to standard BoNT injections.

Methods

In study 1, high‐density surface electromyography (HD‐sEMG) was recorded from the sternocleidomastoid (SCM) and splenius capitis (SC) muscles in 18 CD patients with ongoing BoNT treatment, by which the location of the MEZ was determined. In study 2, nine additional patients with rotational‐type CD participated in a treatment effect study where they received either half of their regular BoNT dose through endplate‐targeted injections or their normal BoNT dose through standard injections (crossover design). Dystonia severity was recorded before and 4 weeks after each treatment session (Toronto Western Spasmodic Torticollis Rating Scale severity subscore).

Results

In the SCM muscle the MEZ was located at the lower border of the superior third part of the muscle, and in the SC muscle at half muscle length. Endplate‐targeted, half‐dosed BoNT injection resulted in a similar treatment effect to injecting the full dose in the standard technique.

Conclusions

Half‐dosed, endplate‐targeted BoNT injections lead to a similar treatment effect to the standard BoNT injection protocol. MEZ detection confronts the clinician with some technical challenges, such as the ability of accurate and technically optimal placement of the electrode grid and correct interpretation of the HD‐sEMG signal.

Original Article

Background and purpose

Patients with prior stroke within 3 months have been mostly excluded from randomized thrombolysis trials mainly because of the fear of an increased rate of symptomatic intracerebral hemorrhage (sICH). The aim of this study was to compare baseline characteristics and clinical outcome of thrombolyzed patients who had a previous stroke within the last 3 months with those not fulfilling this criterion (comparison group).

Methods

In all, 1217 patients were included in our analysis (42.2% women, mean age 68.8 ± 14.4 years).

Results

Patients with previous stroke within the last 3 months (17/1.4%) had more often a basilar artery occlusion (41.2% vs. 10.8%) and less frequently a modified Rankin scale (mRS) score 0–1 prior to index stroke (88.2% vs. 97.3%) and a higher mean time lapse from symptom onset to thrombolysis (321 min vs. 262 min) than those in the comparison group. Stroke severity was not different between the two groups. Rates of sICH were 11.8% vs. 6%. None of the sICHs and only one asymptomatic intracerebral hemorrhage occurred in the region of the former infarct. At 3 months, favorable outcome (mRS ≤ 2) in patients with previous stroke within 3 months was 29.4% (vs. 48.9%) and mortality 41.2% (vs. 22.7%).

Conclusions

In patients with prior stroke within the last 3 months, none of the sICHs and only one asymptomatic intracerebral hemorrhage occurred in the region of the former infarct. The high mortality was influenced by four patients, who died until discharge due to acute major index stroke. It is reasonable to include these patients in randomized clinical trials and registries to assess further their thrombolysis benefit−risk ratio.

Letter to the Editor

Interpretation of post‐anoxic somatosensory evoked potentials − leave it to the experts!

Letter to the Editor

Response to comment: ‘Association between burden and Alzheimer's disease’

Letter to the Editor

Association between burden and Alzheimer's disease

Review Article

Abstract

The purpose was to perform a systematic review of studies on central pontine and extrapontine myelinolysis [forms of osmotic demyelination syndrome (ODS)] and define the spectrum of causes, risk factors, clinical and radiological presentations, and functional outcomes of this disorder. A thorough search of the literature was conducted using multiple databases (PubMed, Ovid Medline and Google) and bibliographies of key articles to identify all case series of adult patients with ODS published from 1959 to January 2013. Only series with five or more cases published in English were considered. Of the 2602 articles identified, 38 case series were included comprising a total of 541 patients who fulfilled our inclusion criteria. The most common predisposing factor was hyponatremia (78%) and the most common presentation was encephalopathy (39%). Favorable recovery occurred in 51.9% of patients and death in 24.8%. Liver transplant patients with ODS had a combined rate of death and disability of 77.4%, compared with 44.7% in those without liver transplantation ( < 0.001). ODS is found to have a good recovery in more than half of cases and its mortality has decreased with each passing decade. Favorable prognosis is possible in patients of ODS, even with severe neurological presentation. Further research is required to confirm the differences found in liver transplant recipients.

Calendar

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Editorial

Recent advances in neurology 2013–2014