As has been well known since the early days of its use in bipolar disorder, lithium has a narrow therapeutic index, with relatively little space between therapeutic and toxic levels. Because of this, avoidance of lithium intoxication has been and continues to be an important goal in treatment. Early reports suggested mortality rates from lithium toxicity ranging from 9 to 25% (Hansen and Amdisen 1978). However, recent data suggest mortality rates of much less than 1% (Baird-Gunning et al. 2016). As an example, in 2012 in the United States, only 11 deaths occurred from 6815 toxic exposures to lithium (Mowry et al. 2013) yielding a mortality rate of 0.16%. Lithium toxicity has been divided into three patterns: acute, acute-on-chronic and chronic with the two latter forms being more dangerous since they are associated with more time to distribute lithium to the CNS intracellular space. In mild lithium toxicity, symptoms include weakness, worsening tremor, mild ataxia, poor concentration and diarrhea. With worsening toxicity, vomiting, the development of a gross tremor, slurred speech, confusion and lethargy emerge (Bauer and Gitlin 2016). Etiologies of lithium intoxication include intentional or accidental overdose, and any factor that alters salt and/or water balance such as the initiation of new medications that alters lithium excretion, dehydration, and infections with fever (Hansen and Amdisen 1978; Haussmann et al. 2015; Ott et al. 2016). Given the potential consequences of lithium toxicity, particular care and vigilant monitoring should be core treatment components with older patients given lithium, since they are more vulnerable to lithium intoxication and at far lower levels than younger patients. Additionally, lithium-treated patients should be queried regularly about their potential use of other medications that may interfere with lithium excretion and, therefore, increase the likelihood of lithium toxicity such as ACE inhibitors, nonsteroidal anti-inflammatory medications such as diclofenac, indomethacin and COX-2 inhibitors such as celecoxib.
Molecular research in the field of ataxia in children is rapidly expanding; on the contrary no similar results have been attained in the field of the treatment since most of the congenital forms remain fully untreatable. Rapid recognition and clinical evaluation of ataxia in children remains of great relevance for therapeutic results and prognostic counseling.
Some advances have been obtained in some of the disorders with ataxia. Treatment of EAs with acetazolamide and GLT1SD with ketogenic diet gave good results [21, 22]. However, a really few hereditary diseases associated with ataxia may be fully treatable. Symptomatic treatment and supportive management may alleviate the course of these severe disorders.
Recognizing ataxia in children may be challenging. It may be overlooked mainly in very young children and erroneously related to a delay of coordination. Physical examination and correct maneuvers are useful for highlighting its clinical sign. The causal events of ataxia are several and have different outcomes that may range from transient and benign to particularly severe and frightening. Pediatricians must be skilled at differentiating treatable disorders from progressive, degenerative and devastating ones, some of which are singularly difficult to diagnose. For most of these disorders, there is no curative care available; only supportive treatment is suitable. A flowchart of the primary causes of ataxia is listed in Fig. 7.
The above research suggests that LSVT LOUD® could be a suitable intervention to treat people with progressive ataxia. However, there is a chance that the technique might not be suitable for all types of ataxic dysarthria, as the presence of concomitant problems such as fatigue, other health problems, and, in some ataxia types, impaired auditory processing or cognitive issues may limit its applicability. Furthermore, it is necessary to establish whether this approach is suitable to address the speech problems experienced by this group of patients, in particular with a view to the spasticity present in some individuals, for which LSVT LOUD® might be counterproductive. Assessments of the suitability of LSVT LOUD® for specific ataxia populations are therefore necessary. Consequently, the aim of our study was to perform a study into the effectiveness and acceptability of LSVT LOUD® to improve communication in people with dysarthria due to progressive ataxias.
One problem that has prevented large trials in this area before is the rare nature of the disorder. With the recent advances in telehealth technology, one way around this issue is to provide assessment and intervention remotely. Research evidence indicating the suitability for this management approach for acquired motor speech disorders is now relatively well established, for both assessment [29, 30] and treatment [31,32,33,34,35,36]. The studies furthermore report high patient satisfaction ratings. However, this research has mostly focused on patients with PD, and with predominantly mild motor difficulties. Issues of usability and acceptability are yet to be investigated for other populations such as people with progressive ataxia, and across a wider severity spectrum, to identify potential barriers that need to be considered.
The study was intended to function as a feasibility study for a larger RCT on the one hand, and already contribute credible evidence towards treatment of dysarthria in progressive ataxia on the other. No previous research was available on this population to enable the calculation of an appropriate sample size. A sample size of 20 was chosen as this was deemed feasible within the available timescale of 15 months and, in addition, aligned with the recommendation of patient numbers for studies following on from single case reports . This permitted us to already contribute the results of this study to the evidence base for treatment of ataxic dysarthria. The treating speech and language therapist (SLT) continuously monitored each patient for adverse reactions to treatment, in order to allow for necessary adjustments to be made to the intervention if necessary. None were reported.
Eligibility criteria for the study included a confirmed diagnosis of progressive ataxia, the presence of ataxic dysarthria, the absence of a functional voice disorder other than can be expected as part of the ataxia, age above 16 years, ability to follow the assessment and treatment tasks, and availability of technology to complete assessment and treatment tasks via Skype.
LSVT LOUD® is an intensive treatment that consists of four 60 min sessions per week over the course of 4 weeks. In addition, home practice is required: 10 min once a day on treatment days and twice a day on non-treatment days . However, an extended version (LSVT-X), consisting of 2 sessions a week over 8 weeks, has been shown to result in comparable speech outcomes . Following consultation with a focus group of four people with progressive ataxia, it was decided to offer participants LSVT-X due to concerns about impact on fatigue levels of the more intense treatment. Sessions generally lasted between 50 and 60 min and followed the prescribed treatment schedule and tasks, and participants were advised to follow the suggested home-practice schedule . As indicated above, LSVT LOUD® focuses on establishing a healthy loud voice, which is often lacking in speakers with PD. Whilst hypophonia has also been reported in people with ataxia, we anticipated that this would not be the case for all study participants. Treatment thus varied depending on the needs of the individual, with a focus on a healthy, unforced voice production for all speakers, and emphasis on a louder voice only for those with symptoms of hypophonia. As part of the aim of this feasibility study was to establish that LSVT would not be harmful to participants, their voice quality and other speech characteristics were carefully monitored throughout the treatment.
To evaluate self-perception and impact of dysarthria pre-therapy, we interviewed participants using the standard pre-treatment questionnaire of the LSVT LOUD® programme, and also asked them to complete the Voice Handicap Index (VHI) , and the short form of the Communication Participation Item Bank (CPIB) . The same questionnaires were used immediately post-treatment (session 3), in addition to a further interview where we discussed changes after treatment as well as experience of the treatment process in relation to schedule, content, and administration by Skype.
Table 1 provides details of patients recruited to the study, including medical history and dysarthria features. As the majority of participants lived a considerable distance from the consulting neurologist and were not due to a routine appointment during the study duration, no up-to-date neurological examination could be conducted as part of this study. Instead, we applied a rough grading of their motor ability as mild (can walk unaided), moderate (needs walking aids), and severe (wheelchair bound). Considering the fact that the feasibility assessment focused on the appropriateness of the speech treatment approach and administration of this via Skype, this was deemed appropriate for the purpose of this study. Table 1 shows that the majority of our participants were rated as showing moderate or severe motor impairment. On the other hand, most had a mild-to-moderate level of speech impairment, with only a few located at the lower moderate to severe end of the spectrum.
Figure 1 provides a visual example of some of the positive changes perceived by the listeners. Figure 1a (participant 1, pre-treatment) shows an unsteady pitch, large variations in loudness, and some aperiodicity of phonation, resulting in a perception of roughness. Figure 1b (participant 1, post-treatment), on the other hand, demonstrates a smoother, more periodic vowel phonation with steady pitch and loudness throughout, reflecting better control of the vocal mechanism. There was again no evidence in an influence of genotype on voice quality, and the range of scores and degree of change from pre- to post-treatment was comparable across participants with FRDA and other types of ataxia. 2b1af7f3a8