[Focal or Segmental Dystonia Resistant to Botulinum Toxin: How Do You Treat Patients in Whom Botulinum Toxin Treatment Has No Effect?]

Botulinum toxin treatment is most commonly used for blepharospasm, spastic torticollis, upper limb dystonia, and local dystonia in Japan. Botulinum toxin treatment is the first choice in these conditions. However, it has the disadvantages that the therapeutic effect is transient, that there are cases in whom the treatment is ineffective, and a high cost. In ineffective cases, botulinum toxin treatment involves medication and rehabilitation. Various medications have been used for the treatment of focal dystonia mainly in open trials. As these treatments have low evidence levels, each case should be dealt with individually. Operative treatment should be considered for severe cases.

Tear meniscus, corneal topographic and aberrometric changes after botulinum toxin-a injection in patients with blepharospasm and hemifacial spasm.

PURPOSE: To investigate the effect of botulinum neurotoxin-A (BTX-A) treatment on dry eye symptoms, tear meniscus, corneal topography and corneal aberrometry in patients with benign essential blepharospasm (BEB) and hemifacial spasm (HFS). MATERIALS AND METHODS: This prospective study comprised of 6 patients with BEB and 20 patients with HFS. Tear meniscus height (TMH) and depth (TMD), tear break-up time (TBUT), corneal fluorescein staining score (CFSS), Schirmer I test, ocular surface disease index (OSDI) score, corneal topography [corneal power of flat axis (K1), corneal power of steep axis (K2), mean corneal power (Km), astigmatism and thinnest pachymetry] and anterior corneal aberrometry [spherical aberration (SA), vertical coma (vcoma), horizontal coma (hcoma), higher order root mean square (hRMS) and total RMS] were evaluated before BTX-A treatment, 3 weeks after BTX-A treatment and 2 months after BTX-A treatment. RESULTS: Six patients with BEB and 20 patients with HFS treated with BTX-A were evaluated in this study. Twenty contralateral spasm free eyes of 20 HFS patients were taken as control group. TMH and TMD were found to be significantly higher in eyes with spasm at both 3 weeks and 2 months after injection (TMH: 279.0 ± 123.2 at pretreatment, 380.5 ± 174.7 at third week and 317.0 ± 125.5 at second month p < 0.001 and p = 0.02, respectively), (TMD: 183.7 ± 59.7 at pretreatment, 235.7 ± 91.1 at third week and 209.8 ± 77.1 at second month p < 0.01 and p = 0.015, respectively). TBUT, CFSS, Schirmer I test values were similar (p > 0.05). OSDI scores decreased significantly from 29.6 ± 25.3 to 19.8 ± 20. p = 0.03 at third week and increased again by second month. K2 (43.9 ± 1.7 vs. 43.7 ± 1.6, p = 0.03) and astigmatism (0.8 ± 0.5 vs. 0.6 ± 0.4, p = 0.04) values were significantly lower at third week and increased again by second month. Pachymetry and aberrometric values did not change significantly. In the control group only Schirmer I test value decreased significantly at second month (10.5 ± 6.5 vs. 7.2 ± 5.6, p = 0.008), other parameters did not change. CONCLUSION: BTX-A injection increases tear meniscus and decrease symptoms related to dry eye disease in BEB and HFS patients. It decrease astigmatism and keratometry values, it does not cause a significant change in corneal aberrations. However the positive effects of BTX-A injection on ocular surface is temporary.

Pregabalin-associated stuttering and frequent blepharospasm: case report and review.

Herpes zoster is an acute, painful, herpes skin disease caused by varicella-zoster virus, which may cause viral meningitis. Pregabalin has been shown to be efficacious in the treatment of pain in patients with herpes zoster. However, it has the side effects of neurotoxicity. We describe a 68-year-old female patient with herpes zoster, and she was treated with pregabalin. The patient presented with stuttering and frequent blepharospasm after 3 days of pregabalin treatment. Pregabalin was discontinued, the symptoms of stuttering and frequent blepharospasm completely resolved without any special treatment after one week. In this case, the etiology of stuttering and frequent blepharospasm may be related to pregabalin. Clinicians should be alert to the rare symptoms associated with the use of pregabalin. Graphical abstract .

Frequency and risk factors of antibody-induced secondary failure of botulinum neurotoxin therapy.

OBJECTIVE: To investigate the risk factors of neutralizing antibody (NAB)-induced complete secondary treatment failure (cSTF) during long-term botulinum neurotoxin (BoNT) treatment in various neurologic indications. METHODS: This monocenter retrospective cohort study analyzed the data of 471 patients started on BoNT therapy between 1995 and 2015. Blood samples of 173 patients were investigated for NABs using the mouse hemidiaphragm test (93 with suspected therapy failure, 80 prospective study participants). The frequency of NAB-cSTF was assessed for various indications: hemifacial spasm, blepharospasm, cervical dystonia, other dystonia, and spasticity. A priori defined potential risk factors for NAB-cSTF were evaluated, and a stepwise binary logistic regression analysis was performed to identify independent risk factors. RESULTS: Treatment duration was 9.8 ± 6.2 years (range, 0.5-30 years; adherence, 70.6%) and number of treatment cycles 31.2 ± 22.5 (3-112). Twenty-eight of 471 patients (5.9%) had NAB-cSTF at earliest after 3 and at latest after 103 treatment cycles. None of the 49 patients treated exclusively with incobotulinumtoxinA over 8.4 ± 4.2 (1-14) years developed NAB-cSTF. Independent risk factors for NAB-cSTF were high BoNT dose per treatment, switching between onabotulinumtoxinA and other BoNT formulations (except for switching to incobotulinumtoxinA), and treatment of neck muscles. CONCLUSIONS: We present a follow-up study with the longest duration to date on the incidence of NAB-cSTF in patients treated with various BoNT formulations, including incobotulinumtoxinA. Whereas the overall risk of NAB-cSTF is low across indications and BoNT formulations, our findings underpin the recommendations to use the lowest possible dose particularly in cervical dystonia, and to avoid unnecessary switching between different formulations.

Report: A case report of Meige syndrome-like blepharospasm caused by ingestion of allopurinol.

One case of allopurinol-caused rare adverse reactions was reported. One male 51-year-old patient presented blurred vision, streaming eyes, photophobia and blepharospasm sequentially 1 week after oral administration of allopurinol. Complete remission was obtained after Botulinum toxin was locally injected. Allopurinol may cause Meige syndrome-like blepharospasm, the mechanism of which may be related to the inhibition of dopamine activity by affecting adenosine level in the brain.

Blepharospasm as a Manifestation of Peak of Dose Dyskinesia in Parkinson Disease.

OBJECTIVES: The aim of the study was to report 4 patients with Parkinson disease (PD) and On-period blepharospasm (BS). METHODS: We analyzed patients with PD and motor fluctuations who developed BS in several different centers in Latin America. RESULTS: Four patients had BS while in the ON periods. CONCLUSIONS: Blepharospasm in the On period in patients with PD is extremely uncommon, and our series is the only one to describe such association.

Hypochlorite accident during wndodontic therapy with nerve damage - A case report.

Endodontic therapy is a routinely practised clinical procedure with few reported complications but, as a bleaching agent, inadvertent spillage of sodium hypochlorite beyond the root canal system may result in extensive soft tissue or nerve damage, and even airway compromise. Although very rare, complications arising from hypochlorite extrusion beyond the root apex are described. NaOCl causes oxidation of protein and lipid membrane and causes necrosis, hemolysis and dermal ulcerations (2-4). Neurological complication are very rare. Paraesthesia and anaesthesia may affect the mental, inferior dental and infra-orbital branches of the trigeminal nerve and normal sensation may take many months to  completely resolve (6, 7). Nerve damage (the buccal branch) was described in 2005 by Witton et al. (8) and patients exhibited a loss of the naso-labial groove and a down turning of the angle of the mouth and the motor function was regained after several months. We present a case in which the extrusion of NaOCl solution during endodontic therapy led to important destructive effects on soft tissues and nerves. The arisen medico legal issues are discussed.

Blepharospasm: an uncommon adverse effect caused by long-term administration of olanzapine.

BACKGROUND: Blepharospasm is one of the components of drug-induced Meige's syndrome which is reported to be caused by typical antipsychotics. Reports of blepharospasm or Meige's syndrome caused by atypical antipsychotics are rare. CASE: A 30-year-old female patient presented to psychiatry out patient department (OPD) with chief complaints of inability to keep her eyes open for long and excessive blinking for 2 months, irritation of eyes, watery discharge from eyes and photophobia for last 1 month. The patient had been taking olanzapine 10 mg, sertraline 100 mg and divalproex sodium 500 mg per orally on once a day basis for the management of major depressive disorder with psychotic features for last 6 months. Routine blood analysis, thyroid function, EEG, MRI, lipid profile did not reveal any abnormality. Ocular examination was also within normal limits. Olanzapine was suspected as a culprit for the above symptoms of patient, so it was replaced with quetiapine 25 mg/day. Patient showed partial recovery of symptoms within 1 week and complete recovery within 2 months of stopping olanzapine. Causality of olanzapine-induced blepharospasm as per WHO-UMC scale was probable. CONCLUSIONS: Olanzapine (atypical antipsychotics) should also be kept in the list of suspected drugs causing blepharospasm in psychotic patients on treatment although further similar evidences from observational studies and/or reports are needed to establish the causal relationship.

Effect of topical administration of tramadol on corneal wound healing in rats.

In this study, we aimed to investigate the effects of topical tramadol administration on corneal wound healing, and examine ophthalmic structures and intraocular pressure 7 days after tramadol administration. The experiments were conducted on eight male Wistar rats (250-300 g). After ophthalmic examination, epithelial cell layers in the central cornea were wounded. Rats received 30 µL of tramadol hydrochloride in one eye (Group Tramadol) and the same volume of vehicle in the other (Group Control) every 12 h for 7 days. Both eyes were stained with fluorescein dye, photographed, and wound area was calculated every 8 h until complete healing was observed. Eye blink frequency and corneal reflex tests were measured before and after drug administrations. After 7 days, slit lamp biomicroscopy, fundoscopy, Goldmann applanation tonometry, and histological evaluation were performed. There was no difference in the corneal wound healing rates between the tramadol and control groups. Reduction in wound area over time was also similar; group-time interaction was insignificant (F = 738.911; p = 0.225). Tramadol application resulted in blinking and blepharospasm for 30 s, but vehicle did not. Corneal reflex was intact and eye blink frequency test results were similar in all measurement times in both groups. Slit lamp biomicroscopy, fundoscopy, and intraocular pressures were within normal range. Corneal cells appeared unaffected by the repeated doses of tramadol for 7 days. Topical tramadol application on the cornea did not cause any side effect, except for initial temporary blinking and blepharospasm. Corneal wound healing was not affected, either.

Glucose hypermetabolism in the thalamus of patients with drug-induced blepharospasm.

We examined the difference in cerebral function alterations between drug-induced blepharospasm patients and essential blepharospasm (EB) patients by using positron emission tomography with (18)F-fluorodeoxyglucose. Cerebral glucose metabolism was examined in 21 patients with drug-induced blepharospasm (5 men and 16 women; mean age, 53.1 [range, 29-78] years), 21 essential EB patients (5 men and 16 women; mean age, 53.0 [range, 33-72] years) and 24 healthy subjects (6 men and 18 women; mean age, 57.9 [range, 22-78] years) with long-term history of benzodiazepines use (drug healthy subjects). Drug-induced blepharospasm patients developed symptoms while taking benzodiazepines or thienodiazepines. Sixty-three normal volunteers (15 men and 48 women; mean age, 53.6 [range, 20-70] years) were examined as controls. Differences between the patient groups and control group were examined by statistical parametric mapping. Additionally, we defined regions of interests on both sides of the thalamus, caudate nucleus, anterior putamen, posterior putamen and primary somatosensory area. The differences between groups were tested using two-sample t-tests with Bonferroni correction for multiple comparisons. Cerebral glucose hypermetabolism on both side of the thalamus was detected in drug-induced blepharospasm, EB patients and drug healthy subjects by statistical parametric mapping. In the analysis of regions of interest, glucose metabolism in both sides of the thalamus in the drug-induced blepharospasm group was significantly lower than that in the EB group. Moreover, we observed glucose hypermetabolism in the anterior and posterior putamen bilaterally in EB group but not in drug-induced blepharospasm group and drug healthy subjects. Long-term regimens of benzodiazepines or thienodiazepines may cause down-regulation of benzodiazepine receptors in the brain. We suggest that the functional brain alteration in drug-induced blepharospasm patients is similar to that in EB patients, and that alteration of the GABAergic system might be related to the pathology of both blepharospasm types.

[Efficacy and side-effects of the botulinum toxin A treatment in patients with focal dystonia].

An aim of the study was to determine side-effects of disport, the botulinum toxin A (BTA), in the treatment of patients with spasmodic torticollis (ST) and blepharospasm (BS). More than 800 injections of BTA to patients with ST and 110 - to patients with BS have been performed for 6-years period. Side-effects are specified as follows: 1) autonomic reactions observed in women with increased anxiety and signs of autonomic dysfunction (47,5%) patients with ST), with most marked symptoms in the first injection and their further decreasing; 2) local side-effects related with errors in dose adjustment, injection technique (37,3% patients with ST and 59,5% patients with BS); 3) the smallest group of side-effects not related to the doctor's experience and adequate psychological preparation of the patient for manipulation (myasthenia-myopathia syndrome after the BTA therapy).

Electroconvulsive therapy and ocular dystonia.

Electroconvulsive therapy (ECT) has been reported to be beneficial in various movement disorders, especially tardive dystonic reactions. In this article, we report an interesting case of drug-induced blepharospasm with ocular dystonia which improved with ECT. To our knowledge, a case of ocular dystonia improving with ECT has not been previously reported in the literature.