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IntroductionFull-thickness rotator cuff tear is present in almost 50% of patients over age 65 years, and its degree is known to be a good predictor of the severity of muscle-wasting (MW) sarcopaenia, also known as fatty degeneration (FD). A FD CT grade > 2° is recognized as a borderline of its reversibility. A disuse model of supraspinatus FD (grade 2) in rabbits provides clinically relevant data. Therefore, the present study evaluates the correlation between eccentric mechanotransduction, neuromuscular transmission (NT), and reversibility of muscle fatty infiltration (MFI) in rabbit supraspinatus FD > 2°.Material and methodsThe supraspinatus tendon was detached from the greater tubercle, infraspinatus, and subscapularis in 16 rabbits. The tendon was reinserted after 12 weeks, and the animals were euthanized 24 weeks after reconstruction. MFI was measured in the middle part of the supraspinatus. Single-fibre EMG (SFEMG) examination of the supraspinatus NT was performed on 4 animals.ResultsThe power of analysis was 99%. Significant differences in MFI volume were found between the operated (4.6 ±1.1%) and the opposite control sides (2.91 ±0.61%) (p < 0.001). SFEMG revealed no significant differences between the disuse and the control supraspinatus muscles (p > 0.05); however, 6.5% of the examined muscle fibres exhibited NT disorders combined with blockade of conduction in 2.5% of muscle fibres.ConclusionsCritical MFI in a disuse model of rabbit supraspinatus FD, CT grade > 2°, is substantially reversible by eccentric training despite subclinical impairment of neuromuscular transmission. In addition, 0.63% reversal of MFI is correlated with 1% hypertrophy of type I and II muscle fibre diameter.

Background Botulinum neurotoxin (BoNT) is an effective treatment for chronic sialorrhea; however, reliable and robust evidence supporting long-term efficacy and safety is lacking. This study investigated the efficacy and safety of repeated incobotulinumtoxinA injections for chronic sialorrhea over 64 weeks. Methods Adults with sialorrhea were randomized (2:2:1) to incobotulinumtoxinA 75 U, incobotulinumtoxinA 100 U (n = 74 each), or placebo (n = 36) in the double-blind, placebo-controlled main period (NCT02091739). Eligible subjects entered the extension period and received dose-blinded incobotulinumtoxinA 75 or 100 U in three further 16±2-week injection cycles. Efficacy and safety assessments in subjects who received incobotulinumtoxinA throughout the study included unstimulated salivary flow rate (uSFR), subjects' Global Impression of Change Scale (GICS), Drooling Severity and Frequency Scale (DSFS), modified Radboud Oral Motor Inventory for Parkinson's Disease (mROMP) drooling, speech, and swallowing symptom scores, and incidence of adverse events (AEs). Results In total, 173/184 subjects (94%) completed the main period and entered the extension period; 141 subjects received incobotulinumtoxinA 75 U (n = 69) or 100 U (n = 72) in both periods. Mean uSFR decreased consistently with repeated incobotulinumtoxinA 75 and 100 U treatment and by −0.16 and −0.17, respectively, at the end-of-study visit. Subjects’ GICS, DSFS, and mROMP drooling scores also improved at all assessments. mROMP speech and swallowing scores remained stable. The most common treatment-related AEs during the extension period were dry mouth (4.4% and 11.1%) and dysphagia (1.5% and 4.2%). Conclusions Data support long-term efficacy and safety of repeated incobotulinumtoxinA treatment for sialorrhea, with no additional safety concerns reported over 64 weeks.

Introduction. The effectiveness of the currently utilized therapies for FoG is limited. Several studies demonstrated a beneficial impact of Nordic walking (NW) on several gait parameters in Parkinson’s disease, but only one paper reported reduction of freezing.Research Question. In the present study, the question is whether NW is an effective therapeutic intervention in FoG.Methods. Twenty PD subjects trained NW for 12 weeks, with a frequency of twice per week. Each session lasted about 60 minutes. Twenty patients in the control group did not use any form of physiotherapy (no-intervention group). Freezing of Gait Questionnaire (FOGQ), the Timed Up and Go (TUG) test, and the Provocative Test for Freezing and Motor Blocks (PTFMB) were performed at baseline, immediately after the end of NW program, and three months later.Results. The results of FOGQ, TUG, and total PTFMB revealed significant improvement after completing the exercise program, and this effect persisted at follow-up. The results of the PTFMB subtests showed a different effect of NW on particular subtypes of FoG. Start hesitation, sudden transient blocks that interrupt gait, and blocks on turning improved considerably, while motor blocks, when walking through narrow space and on reaching the target, did not respond to NW training.Significance. The results show, for the first time, that FoG during turning and step initiation, two most common forms of this gait disorder, has been significantly reduced by NW training. Different responses of particular subtypes of FoG to NW probably reflect their different pathophysiologies.Conclusions. The present study showed that NW training had a beneficial effect on FOG in PD and that the achieved improvement is long-lasting. Future research should clarify whether the observed improvement limited to FoG triggered by only some circumstances reflects different pathomechanisms of FoG subtypes.

The growing number of Botulinum neurotoxin type A (BoNT/A) preparations on the market has resulted in a search for pharmacological, clinical and pharmacoeconomic differences. Patients are occasionally switched from one botulinum toxin formulation to another. The aim of this paper was to review studies that have made direct comparisons of the three major BoNT/A preparations presently on the market: ona-, abo- and incobotulinumtoxinA. We also review the single medication Class I pivotal and occasionally Class II-IV studies, as well as recommendations and guidelines to show how effective doses have been adopted in well-established indications such as blepharospasm, hemifacial spasm, cervical dystonia and adult spasticity. Neither direct head-to-head studies nor single medication studies between all preparations allow the formation of universal conversion ratios. All preparations should be treated as distinct medications with respect to their summary of product characteristics when used in everyday practice.

Objectives: The aim of the paper was to: (1) evaluate the effectiveness of the physiotherapeutic program in writer’s cramp, (2) compare the brain activity while writing in patients with writer’s cramp and in healthy controls, (3) compare the brain activity of subjects with writer’s cramp before and after the physiotherapy. Material and methods: Nine patients with diagnosed writer’s cramp and nine age-matched healthy controls were studied. The functional magnetic resonance imaging while writing was performed in the writer’s cramp subjects and in the controls. The patients with writer’s cramp participated in a 3-week therapeutic program of individualised exercises in combination with the immobilisation of the affected limb. The functional magnetic resonance imaging was repeated after completing the therapeutic program. Results: Only the results of the coil drawing test significantly improved after completing the therapeutic program. All other clinical tests did not reveal any significant changes after the therapy. Activation of primary motor cortex, premotor cortex and primary sensory cortex was observed while writing in the subjects with writer’s cramp and in the controls. Brain activation in clusters located in the areas BA4, BA7, BA18 and BA37 was more pronounced in the writer’s cramp group. Individual analysis revealed a significantly increased activation of the cerebellum in the writer’s cramp patients and it decreased after physiotherapy. Conclusion: In the writer’s cramp subjects, functional magnetic resonance imaging revealed increased – when compared to the controls – activity of several brain structures while writing. This activity was modified by individualised physiotherapeutic program.

Objectives: The purpose of our study was to determine the probability of developing Parkinson’s disease in various syndromes of isolated tremor. Material and methods: We performed a retrospective analysis of the diagnostic process in patients with isolated upper limb tremor where single-photon emission computed tomography (SPECT)-DaTSCAN was performed. Twenty-four consecutive subjects (9 males, 15 females) with isolated tremor of one or both upper limbs were studied. The patients were referred for SPECT by neurologists from various centres. Cases of diagnosed structural, metabolic or druginduced tremor were not included in the study. All patients were examined by a movement disorder specialist before and 1–3 years after SPECT-DaTSCAN. All subjects were classified according to the Consensus Statement on the Classification of Tremors (2018). Results: The lowest probability of developing Parkinson’s disease was found in patients with rest and action (postural and kinetic) tremor, both unilateral and bilateral. The risk was also low in subjects with postural and kinetic tremor. In cases of a combination of rest and postural tremor (both unilateral and bilateral), the likelihood of neurodegenerative parkinsonism was high. Conclusion: Performing SPECT-DaTSCAN in selected cases of isolated of tremor with a high probability of Parkinson’s disease avoids the unnecessary use of drugs recommended in the therapeutic algorithms applicable in essential tremor.

We report here on the ultrastructure of amyloid plaques in chronic wasting disease (CWD) transmitted to Tg20 transgenic mice overexpressing prion protein (PrPc). We identified three main types of amyloid deposits in mCWD: large amyloid deposits, unicentric plaques similar to kuru plaques in human prion diseases and multicentric plaques reminiscent of plaques typical of GSS. The most unique type of plaques were large subpial amyloid deposits. They were composed of large areas of amyloid fibrils but did not form „star-like” appearances of unicentric plaques. All types of plaques were totally devoid of dystrophic neuritic elements. However, numerous microglial cells invaded them. The plaques observed by confocal laser microscope were of the same types as those analyzed by electron microscopy. Neuronal processes surrounding the plaques did not show typical features of neuroaxonal dystrophy.

Holmes’s tremor (HT) is assumed to be the result of coexistence of nigrostriatal dopaminergic system impairment and the lesion of cerebello-thalamic pathways. It was suggested that dopaminergic deficiency is responsible for rest tremor, and lack of compensatory cerebellar function leads to spill of tremor into voluntary movements. Cases of HT with and without abnormalities of the presynaptic part of dopaminergic nigrostriatal were published and these findings raised the question of possibility of the postsynaptic lesion. Three patients with HT diagnosed according to criteria of Consensus Statement on Tremor were studied. In all of them SPECT imaging with ligands of presynaptic (I 123-FP CIT—DaTSCAN) and postsynaptic (I 123-iodobenzamide—IBZM) nigrostriatal dopaminergic neurons was performed. Indices of uptake in caudate and putamen normalized to nonspecific uptake in occipital cortex and indices of asymmetry for each whole striatum as well as for putamen and caudate separately were calculated. SPECT studies did not reveal asymmetry of DaTSCAN and IBZM binding in striatum in all studied subjects. The current clinical diagnostic criteria of HT are presumably insufficiently specific and when using them we identify patients both with and without the involvement of dopaminergic system. These two groups may represent tremor disorders of similar phenomenology but of different pathomechanism.

Aim. Drug-induced parkinsonism (DIP) is the most common form of parkinsonism after Parkinson’s disease (PD) itself. It has been widely believed that DIP is characterised by symmetry of symptoms. Studies of patients with DIP in whom PD had been ruled out by SPECT-DaTSCAN have shown that symptom asymmetry is a common element of DIP clinical presentation. The aim of our study was to determine whether the asymmetry of symptoms in DIP is related to any abnormality within the presynaptic part of the nigrostriatal dopaminergic system. Materials and methods. Eleven patients with the diagnosis of DIP and asymmetric symptoms were studied. Their individual SPECT-DaTSCANs were normal. Indices calculated for the whole group of radiotracer uptake in the whole striatum, putamen and caudate contralateral to more severe DIP symptoms were compared to values obtained in the opposite hemisphere. Results. We did not find significant differences in radiotracer uptake in structures contralateral to more severe clinical symptoms when compared to the homolateral hemisphere. Conclusions. Our results have not confirmed the presence of a presynaptic nigrostriatal deficit which could be related to asymmetry of DIP. The factors responsible for the asymmetry of DIP symptoms should be sought in the postsynaptic part of the nigrostriatal dopaminergic system.

Background. SPECT with radioligand DaTSCAN (SPECT-DaTSCAN) is a sensitive tool used for assessing the functional integrity of the presynaptic part of the nigrostriatal dopaminergic system. The procedure is useful whenever there is a need to distinguish between neurodegenerative parkinsonism and other parkinsonian syndromes in subjects with equivocal signs and symptoms. It can be assumed that the neurologist’s decision to perform SPECT-DaTSCAN depends on his or her experience and skill in the diagnosis of parkinsonian and tremor syndromes. Aims. To assess the accuracy of referrals to SPECT-DATSCAN made by non-movement disorders specialists. Material and methods. Sixty seven patients referred for SPECT-DaTSCAN by a general neurologist were studied. In all subjects, a movement disorder specialist performed the neurological examination, collected medical history, and analysed previous treatments and the results of diagnostic tests. Results. Evaluation carried out by a movement disorder specialist did not confirm an indication for SPECT-DaTSCAN in 31 patients (46.3%). General neurologists needed support for clinical diagnosis with SPECT-DaTSCAN most frequently in subjects with parkinsonism even though they were presenting a full-blown disease manifestation and even though the patients met the diagnostic criteria for Parkinson’s disease or one of the atypical parkinsonian syndromes. Conclusions. Our presented results probably reflect the limited experience of general neurologists in the evaluation of parkinsonian syndromes and tremor. The use of SPECT-DaTSCAN by non-movement disorders specialists is associated with a significant risk of overuse of this tool. To minimise this risk, the skills of general neurologists in diagnosing parkinsonian and tremor syndromes should be improved. Moreover, patients should be provided with access to movement disorders specialists.

10.1016/j.toxicon.2018.11.209

Objective: SIAXI (NCT02091739), a pivotal double-blind, randomised, placebo-controlled study with an extension period (EP), assessed the efficacy and safety of incobotulinumtoxinA 75 or 100 U in patients with sialorrhea due to Parkinson's disease (PD), atypical parkinsonism, stroke or traumatic brain injury. This subgroup analysis assessed the impact of injection guidance technique. Background: Literature suggests that ultrasound (US) guidance of botulinum neurotoxin injections, especially into the submandibular glands, may be needed to improve efficacy and safety. Methods: Patients were randomized (2:2:1) to incobotulinumtoxinA 75 or 100 U, or placebo, distributed in bilateral parotid and submandibular glands in a single injection cycle (IC) in the main period (MP). All eligible patients completing the MP received three further incobotulinumtoxinA ICs (75 or 100 U; each 16+/-2 weeks) in the EP. Injections were consistently guided by US or anatomical landmarks (AL) at investigators' discretion. Outcomes included unstimulated salivary flow rate (uSFR) and patients' Global Impression of Change Scale (GICS). The incidence of adverse events (AEs) was reported. Results: 184 patients were randomised and received either incobotulinumtoxinA 75 U (n=74) or 100 U (n=74), or placebo (n=36) in the MP; 173 completed the MP and entered the EP. In the MP, injections were guided by US in 56.5% of patients and by AL in 43.5%. Among patients treated with incobotulinumtoxinA in all 4 ICs, with US and AL guidance mean uSFR decreased with 75 U and 100 U from study baseline to 4 weeks post-injection, (mean [SD] change from study baseline to end of study: US, -0.15 [0.20] and -0.17 [0.25]; AL, -0.19 [0.22] and -0.17 [0.20]). Patients' GICS also showed improvement at 4 weeks post-injection with both US and AL guidance. The incidence of AEs over all ICs with incobotulinumtoxinA treatment was similar with US and AL guidance (67.0% and 61.0%). The most frequent treatment-related AEs were dry mouth (10.7% and 6.5%) and dysphagia (3.9% and 2.6%). No new safety concerns with respect to guidance technique were reported. Conclusions: In contrast to current literature, repeated incobotulinumtoxinA injections under either US or AL guidance are similarly effective and well tolerated for sialorrhea in patients with PD or other neurological disorders.

iWe report here autophagy in the optic nerve in experimental Gerstmann-Sträussler-Scheinker disease (GSS) (Fujisaki-1) in mice and experimental Creutzfeldt-Jakob disease (CJD) (Echigo-1) in hamsters. Lesions of both experimental GSS in mice and experimental CJD in hamsters were practically indistinguishable. Briefly, they consisted of widespread Wallerian degeneration, spongiform change and a glial reaction. Numerous axonal swellings were seen. The latter were filled with numerous mitochondria and lysosomal electron-dense bodies. Autophagic vacuoles defined as structures bound in double membranes were readily found in many neuronal processes. The following description is organized as a sequence; however, the changes were all observed in the same specimens. First several empty double membrane-bound autophagic vacuoles were seen. In several of those vacuoles, the inner membrane was separated from the outer membrane and enclosed cargo. At the final stage, a mixture of empty autophagic vacuoles and electron-dense lysosomal vesicles was seen. Dystrophic neurites filled with a mixture of mitochondria, empty autophagic vacuoles and electron-dense lysosomal vesicles were interpreted as the final stage of autophagy. Of note, several areas were replaced with dense astrocytic gliosis./i.

Medical treatment of advanced Parkinson disease complicated with fluctuations and dyskinesias remains difficult or in some patients totally ineffective. Recently, new methods were introduced to manage those problems: deep brain stimulation, subcutaneous apomorphine infusion and the Duodopa system for intrajejunal continuous delivery of gel containing levo-dopa/carbidopa (through percutaneous gastrostomy). This last method was proven to be very effective in reducing the fluctuations of levodopa plasma levels and furthermore in reducing the off periods and dyskinesias. The Duodopa system is used in patients with contraindications to deep brain stimulation or apomorphine infusions. According to recently published studies, it may also be more effective in reducing motor complications than other methods. The authors present the current knowledge on the Duodopa system, its effectiveness (also in relationship to other methods, specially deep brain stimulation and apomorphine) and possible complications (mostly due to gastric tube failures) along with the indications and contraindications.

Progressive muscular atrophy (PMA), or the lower motor neuron disease, is a sporadic disorder characterized by onset in adulthood, pure lower motor neuron involvement and relatively benign course. Muscle atrophy and weakness may be symmetrical or asymmetrical, but they are always bilateral. We present a male patient with exclusively left-side flaccid paresis due to lower motor neuron disease without electromyographic evidence of neurogenic lesion of contralateral muscles and with no signs of corticospinal tracts involvement. The rapid disease progression was typical of the generalized phenotype of PMA and it suggested the relation to the aggressive course of classical ALS.

Current antispastic medications are unsatisfactory for spasticity treatment, but botulinum toxin type A (BTX-A) shows promise as a new therapeutic option. This open-label, prospective study aimed to assess the effectiveness of BTX-A in improving functional mobility in the early post-stroke population using an individualised, flexible range of doses and targeted muscle groups. Twenty-one stroke patients (13 male, 8 female) were enrolled and injected with BTX-A (Botox, Allergan, mean dose: 255 U; range: 185-300) according to individual spasticity patterns. Assessments were made at baseline and weeks 2, 4, 6, 10 and 16 post-treatment. Outcome measures comprised: Modified Ashworth Scale (MAS), finger flexion scale (Bhakta), MRC scale, Physician's Rating Scale (PRS), Nine Hole Peg Test (9HPT), Motor Assessment Scale, Clinical Global Impression (CGI), Global Assessment of Spasticity (GASS) and Visual Analogue Scale (VAS) for pain assessment. Statistically significant improvements in muscle tone as determined by the MAS were found in all areas (except arm) till week 16 (p

The supraspinatus tendon was detached from the greater tubercle in 30 rabbits. After 6 weeks (group A), 3 months (group B) and 6 months (group C) in vivo evaluation of the twitch-tension and fatigue index were done. Next the scapulas with muscles were examined by CT. During the first 6 weeks a marked reduction in power and fatigue index by about 20% and 10-15%, respectively, in comparison with the control side was noted. These findings remained unchanged at 3 and 6 months. The CT examination showed fatty muscle degeneration, mainly in the 1/3 distal part of supraspinatus, but not in the infraspinatus muscle.

POEMS syndrome is a rare multisystem disorder, characterized by the presence of polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes. The variety of clinical pictures and asynchronous manifestation of dominant features make diagnosis difficult. We report a case of a 42-year-old man with polyneuropathy who was initially negative for monoclonal protein and so Guillain-Barré syndrome was diagnosed. Other signs and symptoms, including monoclonal gammopathy, developed later in the course of the disease and finally POEMS syndrome was diagnosed.

W ostatnim czasie lista klinicznych zastosowań toksyny botulinowej typu A (BTX-A) znacznie się wydłużyła. Substancja ta stała się narzędziem w rękach neurologów, lekarzy rehabilitacji, urologów, proktologów, migrenologów czy kosmetologów. Zwiększyła się także liczba produkowanych preparatów BTX-A. Obecnie na rynku dostępne są preparaty: Botox, Dysport i Xeomin. Mają one podobny mechanizm działania, aczkolwiek różnią się istotnie budową chemiczną, siłą działania, migracją poza miejsce podania, skutecznością i profilem działań niepożądanych. Te odrębności mogą sprawiać trudności w ich zamiennym stosowaniu przez niedoświadczonego lekarza. Rodzą także pytania o ich równowartość ekonomiczną. Autorzy dokonali przeglądu prac i porównali dostępne preparaty w zarejestrowanych w Polsce wskazaniach neurologicznych. Preparaty te powinny być traktowane jako odrębne leki, a ich zastosowanie kliniczne oparte o dane z badań klinicznych dotyczących poszczególnych preparatów. Recently, the list of clinical applications of botulinum toxin type A (BTX-A) enlarged. This medication is used not only by neurologists, but also by medical rehabilitation specialists, urologists, proctologists, and migraine and aesthetic medicine specialists. Currently, there are three commercially available BTX-A preparations available: Botox, Dysport and Xeomin. They have similar mechanisms of action but their chemical formulation, clinical potency, migration and diffusion as well as safety profile seem to be different. This may result in pro­blems of bioequivalence, not only clinical but also economic ones. The authors reviewed the available clinical and labora­tory studies on neurological indications labelled in Poland. Each BTX-A formulation should be treated as a different medication and used cautiously according to the individual range of dosages established in clinical trials.

Sixteen patients with a clinical diagnosis of subcortical arteriosclerotic encephalopathy (Binswanger's disease) were studied. Mild or moderate dementia was found in 14 cases, with characteristic disturbances of concentration, and psychic retardation with apathy. Neuropsychological studies revealed that signs of diffuse lesions in the frontal lobes dominated. Impairment of memory was significant in all cases. Although intellectual impairment in subcortical arteriosclerotic encephalopathy resembled subcortical dementia, some significant differences were found.

Cerebral vascular amyloid deposits, senile plaques and neurofibrillary tangles have been found in subcortical arteriosclerotic encephalopathy (Binswanger disease). A mouse antiserum, prepared against a 43-amino acid synthetic peptide homologous to the amyloid β-protein of Alzheimer disease (anti-SP43), revealed immunoreactive amyloid deposits in meningeal and intracortical blood vessels, senile plaques, intraneuronal amyloid and preamyloid in a neuropathologically confirmed case of Binswanger disease previously reported to have cerebral vascular amyloid deposits. These lesions contained sulfated glycosaminoglycans as determined by the Alcian blue/critical electrolyte concentration method. Similar findings were not observed in a case of Binswanger encephalopathy without cerebral amyloid deposits. Our study indicates that amyloidotic lesions in Binswanger encephalopathy with cerebral amyloid deposits contain amyloid β-protein and sulfated glycosaminoglycans.

Thirty rabbits were anesthetized, and the supraspinatus tendon was detached from the greater tuberosity and the infraspinatus and subscapularis tendons. After 6 weeks (group A), 3 months (group B), and 6 months (group C), in vivo evaluation of twitch tension and fatigue index was done. Next, scapulas with muscles were examined with computed tomography. The most prominent decrease of twitch tension and fatigue index was noted during the first 6 weeks. The twitch tension and fatigue index after 2 and 4 minutes of the muscle operated on expressed as a percentage of the values developed by healthy contralateral nonoperated muscle were 58.2%, 34.5%, and 32.7% at the beginning of stimulation, 45.4%, 35.3%, and 26.7% after 2 minutes, and 42.5%, 32.6%, and 18.5% after 4 minutes of stimulation, respectively, in groups A, B, and C. Computed tomography examination showed fatty degeneration of the supraspinatus averaging 1.85 (group A), 2.28 (group B), and 2.43 (group C). Moderate infraspinatus fatty degeneration was noted in all groups. There was no significant fatty degeneration of subscapularis muscle. (J Shoulder Elbow Surg 2000;9:211-6.)

Subcortical arteriosclerotic encephalopathy (SAE), or Binswanger's disease, is one of the forms of vascular dementia. In SAE arteriosclerotic changes affect subcortical arteries and arteroles. Atherosclerosis of large cerebral arteries is common among SAE patients. As dyslipoproteinemias are risk factors for atherosclerosis we studied blood lipids and lipoproteins in patients with clinical diagnosis of SAE. In 11 patients diagnosis of the disease was established on the basis of CT scans and clinical course consistent with SAE. In the studied group a tendency to increased total cholesterol and apolipoprotein B and to decreased HDL cholesterol (HDL-CH) were found. The levels of LDL cholesterol (LDL-CH) and the CH/HDL-CH and HDL phospholipides/HDL-CH ratios were significantly higher in SAE patients when compared to controls.

Subcortical arteriosclerotic encephalopathy was diagnosed in a 56-year-old female normotensive patient with gradually progressing dementia, pseudobulbar palsy and motor deficits. CT scan showed white matter low attenuation in the frontal and parietal lobes. Neuropathological examination revealed degeneration of the white matter. Amyloid was found in walls of small cortical vessels. The walls of small vessels in the white matter showed severe thickening, fibrosis and hyalinization but not amyloid. Cerebral amyloid angiopathy may be responsible for subcortical arteriosclerotic encephalopathy.

Two cases of chronic paroxysmal hemicrania are presented, both with atypical late onset of illness and lack of pre-CPH stage. In one patient the pain attacks were unusually short, and no associated symptoms during the pain attack were observed. However, the positive reaction to indomethacin substantiates the diagnosis of CPH.

SYNOPSIS A case of chronic cluster headache with unusually frequent attacks (up to 30 per day) is discussed. Such numerous attacks are usually observed in chronic paroxysmal hemicrania only. The patient did not respond to indomethacin therapy, but rapid improvement during lithium treatment was observed.

ObjectiveThis pivotal phase III study, SIAXI, investigated the efficacy and safety of incobotulinumtoxinA for the treatment of chronic sialorrhea due to Parkinson disease (PD), atypical parkinsonism, stroke, or traumatic brain injury (TBI).MethodsAdult patients with PD (70.7%), atypical parkinsonism (8.7%), stroke (19.0%), or TBI (2.7%) were randomized (2:2:1) to double-blind treatment with placebo (n = 36), or total doses of incobotulinumtoxinA 75 U (n = 74) or 100 U (n = 74), in a single treatment cycle. The coprimary endpoints were change in unstimulated salivary flow rate from baseline to week 4, and patients' Global Impression of Change Scale score at week 4. Adverse events were recorded throughout.ResultsA total of 184 patients were randomized. Both incobotulinumtoxinA dose groups showed reductions in mean unstimulated salivary flow rate at week 4, with a significant difference vs placebo in the incobotulinumtoxinA 100 U group (p = 0.004). Patients' Global Impression of Change Scale scores also improved at week 4, with a significant difference vs placebo in the incobotulinumtoxinA 100 U group (p = 0.002). A lasting effect was observed at week 16 post injection. The most frequent treatment-related adverse events in the incobotulinumtoxinA 75 U and 100 U groups were dry mouth (5.4% and 2.7% of patients) and dysphagia (2.7% and 0.0% of patients).ConclusionsIncobotulinumtoxinA 100 U is an effective and well-tolerated treatment of chronic sialorrhea in adults.ClinicalTrials.gov identifierNCT02091739.Classification of evidenceThis study provides Class I evidence that incobotulinumtoxinA reduces salivary flow rates in patients with chronic sialorrhea due to PD, atypical parkinsonism, stroke, or TBI.