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Background. In 2008, the Movement Disorders Society published the Unified Dyskinesia Rating Scale (UDysRS). This has become the established tool for assessing the severity and disability associated with dyskinesia in patients with Parkinson’s Disease (PD). We translated and validated the Polish version of the UDysRS, explored its dimensionality, and compared it to the Spanish version, which is the Reference Standard for UDysRS translations. Material and methods. The UDysRS was translated into Polish by a team led by JS and GO. The back-translation, completed by colleagues fluent in both Polish and English who were not involved in the original translation, was reviewed and approved by the Executive Committee of the MDS Rating Scales Programme. Then the translated version of the UDysRS underwent cognitive pretesting, and the translation was modified based on the results. The approved version was considered to be the Official Working Document of the Polish UDysRS and was tested on 250 Polish PD patients recruited at movement disorder centres. Data was compared to the Reference Standard used for validating UDysRS translations. Results. The overall factor structure of the Polish version was consistent with that of the Reference Standard version, as evidenced by the high Confirmatory Fit Index score (CFI = 0.98). The Polish UDysRS was thus confirmed to share a common factor structure with the Reference Standard. Conclusions. The Official Polish UDysRS translation is recommended for use in clinical and research settings. Worldwide use of uniform rating measures offers a common ground to study similarities and differences in disease manifestations and progression across cultures.

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.

Botulinum neurotoxin type A (BoNT/A) formulations are widely used in clinical practice. Although they share a common mechanism of action resulting in presynaptic block in acetylocholine release, their structure and pharmacological properties demonstrate some similarities and many differences. Bioequivalence has been discussed since the onset of the clinical use of BoNT/A. In this review, we provide an update on the studies and compare the molecular structure, mechanisms of action, diffusion and spread, as well as immunogenicity and dose equivalence of onabotulinumtoxinA, abobotulinumtoxinA and incobotulinumtoxinA.

Background. In 2008, the Movement Disorders Society (MDS) published a new Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) as the official benchmark scale for Parkinson’s Disease (PD). We have translated and validated the Polish version of the MDS-UPDRS, explored its dimensionality, and compared it to the original English one. Methods. The MDS-UPDRS was translated into Polish by a team of Polish investigators led by JS and GO. The back-translation was completed by colleagues fluent in both languages (Polish and English) who were not involved in the original translation, and was reviewed by members of the MDS Rating Scales Programme. Then the translated version of the MDS-UPDRS underwent cognitive pretesting, and the translation was modified based on the results. The final translation was approved as the Official Working Document of the MDS-UPDRS Polish version, and was tested on 355 Polish PD patients recruited at movement disorders centres all over Poland (at Katowice, Gdansk, Łodź, Warsaw, Wroclaw, and Krakow). Confirmatory and explanatory factor analyses were applied to determine whether the factor structure of the English version could be confirmed in the Polish version. Results. The Polish version of the MDS-UPDRS showed satisfactory clinimetric properties. The internal consistency of the Polish version was satisfactory. In the confirmatory factor analysis, all four parts had greater than 0.90 comparative fit index (CFI) compared to the original English MDS-UPDRS. Explanatory factor analysis suggested that the Polish version differed from the English version only within an acceptable range. Conclusions and clinical implications. The Polish version of the MDS-UPDRS meets the requirements to be designated as the Official Polish Version of the MDS-UPDRS, and is available on the MDS web page. We strongly recommend using the MDS-UPDRS instead of the UPDRS for research purposes and in everyday clinical 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.

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.

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.

The aim of this study was to provide a neurophysiological evaluation of the function of large and small fibers, particularly the peripheral part of the thermonociceptive Aδ pathway in patients with primary restless legs syndrome (RLS).The main evaluation was based on an analysis of the parameters of laser-evoked potentials (LEPs), N2 and P2 components, and an assessment of thermonociceptive thresholds (pain thresholds; PThs). Routine nerve conduction studies (NCS) were also performed.No essential or important differences of clinical significance were observed in the parameters of large fiber conduction between the study and the control groups. Prolonged latencies of N2 and P2 potentials were obtained during foot stimulation in patients with primary RLS when compared to controls (N2, P2-lower right limb, and N2-lower left limb). We also observed higher amplitudes of LEPs evaluated as P2 and N2-P2 potentials in patients with primary RLS in comparison with the control group. Significantly higher (normal distributionOn the basis of the analysis of LEPs and their comparison with the respective results from the control group, the presence of functional disability of the thermonociceptive Aδ pathway was confirmed in patients with primary RLS. The results indicated the presence of changes in the conduction of small fiber pathways in the pathomechanism of idiopathic RLS.

Both disease progression and pulsatile stimulation of dopaminergic receptors are responsible for development of fluctuations and dyskinesia in about 50% of patients with Parkinson disease (PD) after 4-6 years of therapy with levodopa. In order to prevent motor complications, the ideal therapy should secure continuous dopaminergic stimulation (CDS). The concept of CDS is supported by the results of both experimental and clinical studies. Several treatment options are available to achieve CDS. Dopamine agonists have a longer half-life than levodopa and the development of dyskinesia is delayed when they are used as monotherapy in early PD. Continuous delivery of agonists can be improved with prolonged-release oral preparations, a transdermal delivery system or continuous subcutaneous infusion. Continuous enteral infusion of levodopa is another way to achieve CDS and it is very effective in reducing motor complications in advanced PD.

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

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.

Gajos A, Bogucki A, Schinwelski M, Soltan W, Rudzinska M, Budrewicz S, Koszewicz M, Majos A, Gorska-Chrząstek M, Bienkiewicz M, Kuśmierek J, Slawek J. The clinical and neuroimaging studies in Holmes tremor. Acta Neurol Scand: 2010: 122: 360–366. © 2010 The Authors Journal compilation © 2010 Blackwell Munksgaard. Aim – Holmes tremor (HT) is a combination of rest, postural and action tremor. A parallel dysfunction of cerebello-thalamic and nigrostriatal pathways seems necessary to produce this kind of tremor. We present the clinical and neuroimaging study verifying that hypothesis. Material and methods – A total of 10 patients: five male, five female, fulfilling consensus criteria were included. Demographic, clinical and neuroimaging data (MRI = 9; CT = 1, SPECT with the use of 123-I-FP CIT: DaTSCAN in six patients to assess the presynaptic dopaminergic nigrostriatal system involvement, indices of asymmetry for ligand uptake for each striatum were calculated) were analyzed. Results – Hemorrhage was the most frequent etiology and thalamus – the most commonly involved structure. Contrary to the previous reports, the visual assessment did not reveal remarkable interhemispheric differences of DaTSCAN uptake. Quantitative measurements showed only minimal differences. Conclusions – It is open to debate whether nigrostriatal pathway damage is crucial for the phenomenology of HT. Alternative hypothesis is presented that HT represents the heterogeneous spectrum of tremors with similar phenomenology, but different pathophysiology.

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.

Attacks of cluster headache provoked by the administration of nitroglycerin (1 mg sublingually) or histamine (0.01 mg/kg subcutaneously) were studied. The constant latency time in individual patients during nitroglycerin and histamine provocation suggested that the same mechanism is involved in both methods of headache induction. Repeated nitroglycerin provocation revealed its tendency to lengthen duration of the refractory period at the end of the bout, when the attacks were less frequent. The “cross studies” on spontaneous and nitroglycerin provoked attacks indicated that the underlying mechanism of both is at least partially the same.

Serial single fiber electromyography (SFEMG) examinations of orbicularis oculi muscle in patients with blepharospasm or hemifacial spasm treated with botulinum toxin injections were performed. The aim of the study was to evaluate the impairment of neuromuscular transmission, to follow reinnervation after botulinum toxin administration and to find out whether there was a relationship between SFEMG parameters and clinical symptoms. Examinations were performed before injection, during early and late remission of symptoms, and after recurrence of the involuntary movement. Severe impairment of neuromuscular transmission, as revealed by increased jitter and increased presence of abnormal potential pairs and pairs with blocking, was found in early remission, but fiber density remained unchanged when compared with pretreatment values. In late remission, increased fiber density was registered for the first time. The recurrence of involuntary movements was related to the further increase of fiber density and tendency to normalization of jitter parameters. The study therefore suggests that formation of new neuromuscular junctions and their functional maturation is responsible for muscle recovery after botulinum toxin administration.

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.

Thirty-two cluster headache patients and healthy controls (n = 16-20 for the various tests) were examined by means of a Whitaker pupillometer during pain-free intervals. Eye drops of the sympathomimetic agents tyramine, hydroxyamphetamine, and phenylephrine were instilled into the conjuctival sacs on separate occasions, and pupillary diameters recorded at standard time intervals. The mydriatic responses of the two pupils were compared. A moderate, but statistically significant, basal relative miosis was found on the pain side in cluster headache. The symptomatic-side pupils were less responsive than their counterparts when stimulated with tyramine and hydroxyamphetamine, the difference being statistically significant for the OH-amphetamine test. With the phenylephrine test, however, the mydriasis on the symptomatic side significantly exceeded that of the contralateral pupil. This pattern of reactions does not quite correspond to those of “ordinary” Horner‘s syndrome (1st, 2nd, and 3rd neuron lesion). There are, however, gross similarities with the recently reported pattern in central sympathetic neuron dysfunction. In cluster headache there is probably a “Homer-like picture” rather than a proper Horner's syndrome.

Eight patients with Horner's syndrome (five with a 1st neuron lesion and three with a 2nd neuron lesion) were examined for their pupillary responses to pharmacologic stimulation with tyramine (2%) and with phenylephrine (1%) eye drops. The same patients were also evaluated for their forehead sweating pattern on stimulation with body heating and pilocarpine injection, using the Evaporimeter. Five patients had a brain stem (1st sympathetic neuron) lesion, while three patients had had a traumatic C8-Th1 root avulsion and hence had a preganglionic neuron lesion. The average response with the phenylephrine eye test and the pilocarpine sweat test differed markedly between the two groups; only the central neuron lesion group had a supersensitivity reaction to both drugs. These procedures may be of diagnostic value in localizing the lesion in patients with a Horner's syndrome of unknown etiology. Patients with 3rd neuron lesion have not been examined with this combination of techniques.

Eleven female patients with cervicogenic headache (mean age, 43 years; range, 25–59 years) have been examined with the pupillometer. The pupillary diameter was examined in the basal state (that is, the status before pharmacologic stimulation) and after topically administered tyramine (2%), phenylephrine (1%), and hydroxyamphetamine (1%). A total of 51 tests were performed, 35 in the asymptomatic period and 16 during pain attacks. In a control group consisting of 26 age-matched women a total of 39 tests were carried out. Before pharmacologic stimulation (that is, in the “basal state”) the pupils were smaller in the asymptomatic (pain-free) period than during pain attacks in the patients and also as compared with that of control individuals. The anisocoria (the difference in pupillary size in the same individual) observed was not significantly different between the patient group and control individuals either in the basal state (before pharmacologic stimulation) or after pharmacologic stimulation. The mydriasis resulting from the instillation of the three sympathicomimetic drugs was symmetrical in both controls and patients both during and between the pain attacks. This finding is in clear contrast to what is found in cluster headache, in which there is a “Horner-like” syndrome on the symptomatic side. These two headaches thus seem to differ essentially with regard to this variable.

Histamine skin tests were performed in the painful area and on the opposite side in ten cluster headache patients. The studies were carried out with and without local anaesthesia. No differences between histamine skin response in the painful region compared with the contralateral side were revealed. This study concerns the part of the triple response which is the result of a direct action of histamine on the skin vasculature (mediated by both H1 and H2) histaminergic receptors, i.e. wheal and redness, and the flare, which is the result of neuro-humoral mechanisms.

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.