Monday, January 26, 2015

Ataxia & Sleep Disorders - What do we know?

Ataxia and Sleep Disorders

Sleep disorders may be due to ataxic disorders AND can exacerbate them. If you have trouble sleeping, daytime sleepiness or your doctor.  _JR

Arquivos de Neuro-Psiquiatria

Arq. Neuro-Psiquiatr. vol.69 no.2a São Paulo Apr. 2011 


Sleep disorders in cerebellar ataxias

Distúrbios do sono nas ataxias cerebelares

José L. Pedroso; Pedro Braga-Neto; André C. Felício; Camila C.H. Aquino; Lucila B. Fernandes do Prado; Gilmar Fernandes do Prado; Orlando G.P. Barsottini
Department of Neurology and Neurosurgery, Universidade Federal de São Paulo, São Paulo SP, Brazil

Cerebellar ataxias comprise a wide range of etiologies leading to central nervous system-related motor and non-motor symptoms. Recently, a large body of evidence has demonstrated a high frequency of non-motor manifestations in cerebellar ataxias, specially in autosomal dominant spinocerebellar ataxias (SCA). Among these non-motor dysfunctions, sleep disorders have been recognized, although still under or even misdiagnosed. In this review, we highlight the main sleep disorders related to cerebellar ataxias focusing on REM sleep behavior disorder (RBD), restless legs syndrome (RLS), periodic limb movement in sleep (PLMS), excessive daytime sleepiness (EDS), insomnia and sleep apnea.

Key words: sleep disorders, ataxias, diagnosis.

As ataxias cerebelares se caracterizam por uma enorme variedade de etiologias, cursando tanto com sintomas motores como também com sintomas não motores. Recentemente, várias evidências têm demonstrado uma frequência elevada de sintomas não motores nas ataxias cerebelares, especialmente nas ataxias espinocerebelares autossômicas dominantes (SCA). Dentre os sintomas não motores, estão os distúrbios do sono, que muitas vezes são sub-diagnosticados ou pouco valorizados. Nessa revisão, enfatizamos os principais distúrbios do sono relatados nas ataxias cerebelares, como transtorno comportamental do sono REM, síndrome das pernas inquietas, movimentos periódicos das pernas no sono, sonolência diurna excessiva, insônia e apnéia do sono.
Palavras-chave: distúrbios do sono, ataxias, diagnóstico.

Cerebellar ataxias comprise a wide range of neurodegenerative, congenital, mitochondrial, and metabolic diseases leading to central nervous system-related motor and non-motor dysfunctions1. Among these non-motor dysfunctions, sleep disorders have been recognized, although still under or even misdiagnosed. Their pathogenesis may be secondary to direct structural alterations of the sleepwake generating cells and networks or be the consequence of several indirect mechanisms1. Recently, a large body of evidence have demonstrated that non-motor manifestations are much more frequent than previously thought not only in autosomal dominant spinocerebellar ataxias (SCA), but also in several other neurodegenerative diseases such as synucleinopathies (Parkinson's disease, Lewy body dementia and multiple system atrophy), taupathies (Alzheimer's disease, frontotemporal dementia, corticobasal degeneration, progressive supranuclear palsy), amyotrophic lateral sclerosis, and prion diseases1.

The most frequent recognized sleep disorders in patients with neurodegenerative diseases are insomnia, hypersomnia, parasomnias, excessive nocturnal motor activity, circadian sleep-wake rhythm disturbances, respiratory dysrhythmias and sleep apnea1. It is crucial to recognize sleep disorders in neurodegenerative diseases not only to make an earlier diagnosis, but also to improve the quality of life1,2. In this review, we highlight the main sleep disorders related to cerebellar ataxias focusing on REM sleep behavior disorder (RBD), restless legs syndrome (RLS), periodic leg movement in sleep (PLMS), excessive daytime sleepiness (EDS), insomnia and sleep apnea1,3.

Sleep disorders in autossomal dominant SCAs
SCAs have been defined as a group of autosomal dominant ataxic disorders caused by degeneration of the cerebellum and its afferent and efferent connections. The majority of SCA are also complicated by the presence of additional neurological signs and non-motor symptoms, such as sleep disorders4. Additionally, extra-cerebellar alterations vary between genotypes4.
Sleep complaints, particularly RLS and PLMS, have been observed in some forms of SCAs, with a higher frequency in SCA1, SCA2, SCA3 or Machado Joseph disease (SCA3/MJD), and SCA61,5,6. Available evidence shows that the frequency of RLS in SCAs is significantly greater than in the general population ranging from 20 to 30%6. In line with this we describe in the following section the most frequent sleep disorders seen mainly in SCAs 1,2,3 and 6.
Spinocerebellar ataxia type 1 (SCA1): RLS has been poorly reported in patients with SCA 1. Among the few data available the frequency of RLS in patients with SCA1 is estimated to be 23% in a small sample6. Another study showed a similar frequency, but with even fewer patients. One study pointed out to a lack of association between RLS and periodic limb movement on polysomnography5. Interestingly, one study did not show evidence for RLS in SCA1 showing that the frequency actually varies according to patient selection or study methodology5,6.Recently, EDS and fatigue were also reported in two individuals with SCA1, suggesting that EDS in SCA1 may be an inherent consequence of the neurodegenerative disorder itself, and wake-promoting agents may be of benefit7.
Spinocerebellar ataxia type 2 (SCA2): RLS has been described in patients with SCA2, and frequency ranges between 18 and 27%5,6. Moreover, two previous studies have shown RBD in SCA2 patients characterized with REM without atoniaand mioclonic jerks8,9. PLMS had a higher frequency in just one of the studies9.
Spinocerebellar ataxia type 3 or Machado Joseph disease (SCA3/MJD): SCA3/MJD is the most common autosomal dominant-subtype of ataxia worldwide4,10. The disease comprises a wide range of clinical manifestations, which include cerebellarataxia, parkinsonism, dystonia, peripheral neuropathy, pseudoexophthalmos, lowermotor neuron disease, with fasciculations and amyotrophy10. Recent studies also point out for a more diffuse neurodegeneration, which better explains the non-motor symptoms of the disease and possibly under-recognized, such as sleep disorders, memory deficits and executive impairment, olfactory dysfunction and psychiatry disturbances (Table 1)11. In addition, the cerebellum itself has also been involved in non-motor functions. Recent clinical data has demonstrated high incidence of sleep complaints in SCA3/MJD12. Likewise, sleep complaints have been considered as an important modifier of health-related quality of life in SCAs12. The most frequent reported sleep complaints in SCA3/MJD are RLS13, RBD14, EDS14, sleep apnea12, and insomnia12. Curiously, not only these sleep disorders might be a frequent non-motor symptom in SCA3/MJD, but may also precede the onset of cerebellar symptoms2.

When we consider SCA3/MJD patients, frequency rates of RLS are high, reaching about 55% in several studies12,14,15. Regarding the dopaminergic system dysfunction of primary RLS, it is speculated that RLS could reflect basal ganglia impairment in patients with SCAs5. Also, RBD has a higher frequency in SCA3/MJD patients when compared to the general population, reaching up to 50%12. The underlying involvement of midbrain cholinergic and pontine noradrenergic systems seen in SCA3/MJD patients could in part explain these higher rates of RBD2,3. Likewise synucleinopathies, RBD and RLS may precede any other clinical manifestation of cerebellar symptons by more than 10 years2.
High frequencies of EDS have been documented in SCA3/MJD patients12,14. Furthermore, in some series, insomnia was the most frequently reported sleep disorder12. There is also a higher frequency of sleep apnea in SCA3/MJD than in general population ranging from 20 to 25%12. Patients who reported snoring and possible apnea during sleep had longer disease duration and were older12. Moreover, hypnagogic hallucinations are more related in SCA3/MJD patients than healthy subjects12. Figure describes some polysomnographic features in a patient with SCA3/MJD.

Spinocerebellar ataxia type 6 (SCA6): One study found a marked increase in PLMS indices in five patients with SCA6. Interestingly, all patients had a normal nerve conduction study excluding peripheral neuropathy as a cause of their limb complaints. The same study showed RLS in two of 5 patients and no RBD16. A larger study with 21 SCA6 patients found only one patient with RLS and sleep apnea13.
Table 2 is a brief summary of many studies concerning sleep disorders found in different SCAs subtypes. We have not found enough data to inform the frequency of sleep disorders in the SCAs other than SCA 1, 2, 3 and 6, although some sporadic reports are available in the literature.
Sleep disorders in recessive ataxias
Recessive ataxias may be divided into five groups: Congenital, mitochondrial, metabolic, degenerative, and related to defects in DNA repair17. A limited number of data is available concerning sleep disorders in recessive ataxias.
Among congenital ataxias, Joubert syndrome and related disorders (JSRD) are the most remarkable. This term is adopted to describe a group of diseases that presents the "molar tooth sign" in brain imaging. JSRD is typically characterized by hypotonia, ataxia, respiratory disturbances, and abnormal ocular movements. The typical respiratory abnormalities are represented by episodes of apnea and/or hyperventilation that can range since from brief periods of hyperpnea until long attacks of apnea18. Although first described in awake state, the respiratory abnormality can occur during sleep. It has been described a sleep disordered breathing manifesting as repetitive tachypnea followed by central apnea, and isolated tachypnea during asleep, interestingly detected only in non-REM sleep19.
Friedreich ataxia (FA) is the commonest recessive ataxia worldwide, manifesting as progressive sensory and cerebellar ataxia, arreflexia, Babinski sign, often associated with cardiomyopathy, scoliosis and pes cavus17. Data on sleep disorders in patients with FA is poor. It has been published a case of mixed apnea, with obstructive and central apnea in one patient with late stage FA20.
A polysomnographic study in twelve patients with ataxia telangiectasia, a recessive disease that causes not only ataxia, but also cutaneos telangiectases, immunodeficiency, sino-pulmonary infections and lymphoreticular malignancies, was conducted to evaluate the patterns of sleep and respiration during sleep. The authors found decreased sleep efficiency when compared to normal values, eight patients with obstructive apnea and hypopnea, and four with central apnea, approximately half of them with oxygen desaturations21.
Despite the lack of enough previous studies concerning sleep disorders in recessive ataxias, we realized that the main sleep complaints are related to breathing. Therefore, physicians should be aware about sleep-breathing disorders in recessive ataxias and polysomnography study should be promptly performed in this situation.

Sleep disorders in sporadic ataxias
Multiple system atrophy (MSA) is a sporadic neurodegenerative disease characterized clinically by various combinations of cerebellar, parkinsonism, autonomic and pyramidal symptoms or signs. Pathologically is characterized by cell loss, gliosis and glial cytoplasmatic inclusions in several brain and spinal cords structures22. When cerebellar ataxia is the dominant clinical feature, the disease is termed MSA-C. The signs of cerebellar dysfunction include disorders of extraocular movements, ataxia of speech, ataxia of limbs movements and gait22.

MSA patients have multiple sleep-related disorder symptoms including EDS, insomnia, arrhythmic respiration, sleep apnea, RBD, and sleep-related stridor with vocal cord paresis23. OSA and central sleep apnea frequently occur in MSA and may cause sudden death. RBD is closely related to neurodegenerative disorders, specially the synucleinopathies, and may precede motor symptoms of PD or MSA by years24. It has been demonstrated that REM sleep behavior disorder may precede other aspects of synucleinopathies by up to 25 years25. Another data comparing sleep disturbances in patients with PD, MSA and PSP demonstrated that patients with MSA showed higher risk of OSA and less frequent RLS26. The PRIAMO study, which analyzed non-motor symptoms in atypical and secondary parkinsonism, found that sleep disturbances were also common with a prevalence of approximately 70% in all diagnostic groups, including MSA patients27.

RBD and nocturnal stridor are considered red flags and may be the first symptoms of the disease22. Sleep-disordered breathing manifests as [1] central hypoventilation that reflects impaired automatic control of ventilation secondary to degeneration of the pontomedullary respiratory centers; and, more commonly, as [2] stridor and obstructive sleep apnea due to larynx narrowing secondary to combined vocal cord abductor paralysis and excessive adductor activation during inspiration23.
The recent identification of fragile X-associated tremor ataxiasyndrome (FXTAS) associated with premutations in the FMR1 geneand the possibility of clinical overlap with multiple systematrophy has raised important questions. These neurodegenerative diseases may have similar clinical presentations, including sleep disorders28.

Alexander disease (AD) in its typical form is an infantile lethal leucodystrophy, characterized pathologically by Rosenthal fibers accumulation. Detailed clinical and genetic data from one study of 11 cases of adult-onset AD showed that the most frequent symptoms were related to bulbar dysfunction with dysarthria, dysphagia, dysphonia, pyramidal involvement and cerebellar ataxia. Sleep disorders were also observed in four cases29.

Sporadic fatal insomnia is a rare prion disease that has recently been recognized and is characterized by loss of sleep, oneiric stupor with autonomic/motor hyperactivity and somato-motor abnormalities, including pyramidal signs, myoclonus, dysarthria, dysphagia and ataxia30. In the new variant of Creutzfeldt-Jakob disease some patients demonstrated a combination of psychiatric symptoms, ataxia and severe sleep disorders31.

Although still unrecognized sleep disorders in cerebellar ataxias have been a recent issue of interest, and growing evidence has proving the importance of their identification. Not only because sleep disorders in cerebellar ataxias may precede the onset of motor symptoms, but also due to its impact in the health-related quality of life.

A similar problem found in the studies aforementioned is that the numbers of patients already evaluated are too small to conclude specific patterns of sleep disorders in a single group of cerebellar ataxias, for instance SCA3, and also limited information on the exact frequency of these sleep-complaints limits a full data interpretation. Therefore, future studies addressing sleep disorders in a large sample population with cerebellar ataxias are welcome. Additionally, a standardized assessment of these patients should be considered to allow data comparisons within different research centers.

Why do serotonergic medications help some ataxias?

Why do serotonergic medications help some ataxias?

 2001 Jun;7(3):207-19.

Serotonergic neuromodulation in the cerebellar cortex: cellular, synaptic, and molecular basis.


    The cerebellum, like most sensorimotor areas of the brain, receives a serotonergic innervation from neurons of the reticular formation. It is well established that local application of serotonin modulates the firing rate of cerebellar Purkinje cells in vivo and in vitro, but the mechanisms by which serotonin affects the cerebellar function are still poorly understood. Whereas interactions between serotonin, glutamate, and GABA have been reported to increase or decrease the firing frequency of Purkinje cells, there is little evidence for a modulation of excitatory and inhibitory synapses by serotonin in the cerebellar cortex. 
     Changes in the intrinsic electrical properties of Purkinje cells upon application of serotonin have also been reported, but their impact on Purkinje cell firing is unclear. The recent finding that serotonin specifically modulates the activity of Lugaro cells, a class of inhibitory interneurons of the cerebellar cortex, offers new insights on the action of this neuromodulator. The peculiar axonal projection and specific interneuronal targets of the Lugaro cells suggest that the action of serotonin might occur upstream of Purkinje cells through a resetting of the computational properties of the cerebellar cortex. 
       Understanding the mechanisms of the serotonergic modulation of the cerebellar cortex is of clinical relevance, as abnormal serotonin metabolism has been observed in animal models and pathological cases of motor disorders involving the cerebellum, and as chronic intravenous administration of L-5-hydroxytryptophan (5-HTP), a precursor of serotonin, was the first treatment shown to improve significantly cerebellar symptoms.

 1993 May;20 Suppl 3:S78-82.

The cerebellar serotoninergic system and its possible involvement in cerebellar ataxia.


A review concerning the characteristics of the cerebellar serotoninergic system is presented. In rat, cat and oppossum, the perikarya of origin are located in the brain stem raphe nuclei and in other brainstem structures. The projections to the cerebellar layers and deep nuclei include synaptic connections, but also non synaptic terminals, especially in a diffuse cortical plexus. Serotoninergic receptors have been described: 5-HT1B in the molecular layer and 5-HT2 in the inferior olive. Serotonin exerts neurophysiological effects on several target cells, directly or indirectly, presynaptically or postsynaptically. A modulatory effect on Purkinje cells is well documented. In thiamine deprived animals, a specific serotoninergic cerebellar syndrome includes a selective degeneration of the serotoninergic cerebellar system, an increase of the 5-HIAA cerebellar values and an exaggerated serotoninergic turnover. In human heredoataxias (Friedreich's ataxia and cerebellar cortical atrophy), serotoninergic disturbances have been observed in the CSF, including low 5-HIAA values and an increased serotoninergic turnover. Therapeutic results have been obtained with L-5-HTP, a precursor of serotonin, in several conditions presenting cerebellar ataxia. L-5-HTP resistance of olivopontocerebellar atrophies may be explained by the destruction of serotonin-sensitive target cells, especially Purkinje cells.

Saturday, January 24, 2015

Are circumcised boys more likely to develop autism? More Fear-Mongering.

Oh no! The anti-circumcision folks have gotten on the autism train.    A study out of Denmark claims that boys who are circumcised are more likely to develop autism than boys who are not circumcised. 

First, the article does not assess socioeconomic status as a confounder. Data shows that this makes a difference in non-religious circumcision choice. It did not control for parentla age. Another risk factor.

Second, what factors lead to an autism diagnosis in Denmark? Could there be a double SES selection bias? 

Third. This study was of "KKGV20" ritual circumcision performed in private clinics and billed ot the government. Really? 

Read the following "The increased risk of ASD in circumcised boys under the age of 5 years was present among boys in both Muslim and non-Muslim families (Table 2). Risk in this age group was markedly elevated among boys in non-Muslim families (HR = 4.23; 95% CI: 1.90–9.44), a finding based on six ASD cases in circumcised boys versus 1165 cases in intact boys. " Ok. Look at the table (no one does) when you consider the 0-9 group as a whole, suddenly the statistic is not significant HR 1.18 (95% CI .56-2.48).

My guess is that this fits into the anti-circumcision screeds in Europe right now. 

If this had any merit, one might expect all Jews and other people practicing this universally to have higher rates of autism?

International demograpics by WHO


Research published today by the Journal of the Royal Society of Medicine suggests that circumcised boys are more likely than intact boys to develop autism spectrum disorder (ASD) before the age of 10. Risk is particularly high for infantile autism before the age of five. The research was carried out in Denmark among a cohort of all children born between 1994 and 2003. During the study over 340,000 boys were followed up to the age of nine between 1994 and 2013 and almost 5,000 cases of ASD were diagnosed. The study showed that regardless of cultural background circumcised boys may run a greater risk of developing ASD. The researchers also made an unexpected observation of an increased risk of hyperactivity disorder among circumcised boys in non-Muslim families.
Professor Morten Frisch of the Statens Serum Institut, Copenhagen, who led the research, said: "Our investigation was prompted by the combination of recent animal findings linking a single painful injury to lifelong deficits in stress response and a study showing a strong, positive correlation between a country's neonatal male circumcision rate and its prevalence of ASD in boys."
Today it is considered unacceptable practice to circumcise boys without proper pain relief but none of the most common interventions used to reduce circumcision pain completely eliminates it and some boys will endure strongly painful circumcisions. The researchers say that the pain associated with circumcision in very young babies is likely to be more severe during the operation and post-operatively.
Painful experiences in neonates have been shown in animal and human studies to be associated with long-term alterations in pain perception, a characteristic often encountered among children with ASD.
"Possible mechanisms linking early life pain and stress to an increased risk of neurodevelopmental, behavioural or psychological problems in later life remain incompletely conceptualised," said Professor Frisch. "Given the widespread practice of non-therapeutic circumcision in infancy and childhood around the world, our findings should prompt other researchers to examine the possibility that circumcision trauma in infancy or early childhood might carry an increased risk of serious neurodevelopmental and psychological consequences."
Read more here

Friday, January 23, 2015

Does botox cause atrophy or hypertrophy following injections for cerebral palsy? What does the data say?

Is there atrophy, hypertrophy both? Does it matter? Having injected since 2000, I agree with the observation that early and aggressive botox  with multilevel tendon lengthening at an older age reduces crouch gait. Careful injection placement with an experienced practitioner is probably the wisest choice. JR

Atrophy and hypertrophy 

following injections of 

botulinum toxin in 

children with cerebral palsy

  1. Tandy Hastings-Ison1 and
  2. H. Kerr Graham2
Article first published online: 16 JUL 2013
DOI: 10.1111/dmcn.12231

Since the first report of the use of botulinum toxin A (BoNT-A) in the management of children with cerebral palsy (CP) in this journal almost 20 years ago, the drug has been licensed in many countries. It is now widely used and considered by many to be a ‘standard of care’.[1] With more widespread use has grown an appreciation of both its benefits and risks, leading to an urge for caution. Fortunately, serious adverse events and deaths following injection of BoNT-A are rare and preventable so long as risk factors which reside within the child are recognized and appropriate dose and administration guidelines are observed.

However, a more insidious and silent problem may be post-injection muscle atrophy, reported by Williams et al.[2] In contrast to the alarming reports from animal studies, which include substantial reductions in muscle mass and force generation,[3] the results in children with CP are quite different and broadly reassuring. Williams et al. report a study of 15 children, aged 5 to 11 years with spastic diplegia, at Gross Motor Function Classification System levels I and II, who received injections of BoNT-A to the gastrocnemius muscles in both lower limbs, and in some patients to the medial hamstring muscles when clinically indicated. Muscle volumes were computed from magnetic resonance imaging (MRI) and Mimics software at 2 weeks prior to injection and 5 weeks post-injection. Although the volume of the gastroc soleus muscle group remained unchanged, there was a 5% reduction in gastrocnemius muscle volume and a 4% increase in soleus volume following BoNT-A injection. In addition, significant quadriceps hypertrophy was also found, interestingly only in the group who did not receive injection to the hamstring muscles. The atrophy of the gastrocnemius is much smaller than that reported in rabbit quadriceps and is consistent with the known effects of the toxin. The hypertrophy of the soleus and the quadriceps is a novel finding and may represent a compensatory strategy secondary to muscle and/or nervous system plasticity. Importantly, there was no evidence of impaired function in the injected children.[2]

What does this mean for the practicing clinician? Firstly, with appropriate injection techniques, atrophy of the target muscle is reasonably limited and may to some degree be compensated for by hypertrophy in neighbouring muscles. However, given that spastic diplegia is associated with a 22% smaller medial gastrocnemius muscle volume as part of the natural history,[4] any additional atrophy would be a matter for concern. Furthermore, new evidence has found medial gastrocnemius growth rate to be slower in children with CP compared with typically developing peers, with a further 60% reduction following BoNT-A injection.[5]

Obtaining serial MRI is difficult in younger children because of compliance issues and expense. The authors and the children in the study should be congratulated on completing this demanding protocol. As always, more studies, larger numbers, and longer-term follow-up hold the key to improved understanding of the muscle responses in growing children to injections of this widely used therapy. How much BoNT-A and how frequent is not well established.

In spastic diplegia, the two-joint gastrocnemius is more implicated in gait dysfunction than the one-joint soleus. Preserving soleal strength and moment generating capacity is critical to long-term walking ability and in preventing crouch gait. In older children with fixed contractures, the most common intervention is a gastrocnemius recession in which the soleus is not lengthened and its function is preserved. It is fascinating that the results of this study suggest that similar effects can be achieved by selective injection of the gastrocnemius, that is atrophy of the gastrocnemius and preservation of the soleus. Non-ionizing imaging techniques, including both three-dimensional ultrasound and MRI, hold great promise in the understanding of muscle biomechanics and the response to intervention.[4, 5]

Finally, it is important to consider the broader context of gait management in children with spastic diplegia in the first decade of life.

Prior to the introduction of BoNT-A, gastrocsoleus lengthening was often utilized in very young children with spastic diplegia.  This resulted in an alarming degree of progressive crouch gait which in many cases resulted in more functional disability and required more complex surgical reconstruction than the original equinus gait problem.

With the introduction of BoNT-A injections to the gastrocsoleus, followed by multilevel surgery at an appropriate age, the prevalence of crouch gait has been dramatically reduced in our centre.

Article here

I am often asked about the long term efficacy

 2014 May;121(5):521-30. doi: 10.1007/s00702-013-1145-3. Epub 2014 Jan 10.

Spasticity treatment with onabotulinumtoxin A: data from a prospective German real-life patient registry.


This study aimed at providing real-life baseline, injection and outcome data for the treatment of various forms of spasticity with onabotulinumtoxin A in Germany. 

Prospective data were collected in an open multicenter patient registry from 2005 until 2010, encompassing the experience of ten specialized German centers in the treatment of spasticity using onabotulinumtoxin A in 508 patients with a total of 2005 treatment sessions. 

Disease entities comprised spasticity following stroke (both ischemic and hemorrhagic), traumatic brain injury, multiple sclerosis, cerebral palsy, and anoxia. Sustained improvement was observed in a variety of outcome parameters including goal attainment and motor performance scores for up to five repeated injection sessions.

No significant differences between disease entities or between upper and lower limb treatment were observed with regard to efficacy and safety following onabotulinumtoxin A treatment. 

Minor to moderate side effects were reported in <1 nbsp="" of="" population.="" span="" study="" the="">

We conclude that repetitive treatment of focal and multifocal spasticity with onabotulinumtoxin A provides a safe and efficacious therapeutic strategy for patients with different disease entities of the central nervous system.

 2014 Feb;29(2):210-3. doi: 10.1177/0883073813495306. Epub 2013 Aug 21.

Botulinum toxin type A in children and adolescents with severe cerebral palsy: a retrospective chart review.


This retrospective cohort study reviewed set goals and their outcomes of children and adolescents with severe cerebral palsy who received botulinum toxin A in 2008 and 2009. Sixty children (36 male, mean age 9 years) were included. They received on average 4 (range 1-7) treatments, with the dosage varying between 20 and 400 units per treatment (3-21 U/kg/body weight). Mild transient side effects were reported in 12 of 242 treatments with botulinum toxin A. Treatment goals were related to lower limb function (82%), range of motion (68%), positioning (33%), upper limb function (33%), and facilitating ease of care in dressing (30%), toileting, and diapering (22%). The treatment goals were reached in 60% to 85% by report of the parent and child dyad. Our findings suggest that botulinum toxin A should be considered as a treatment option in patients with cerebral palsy within Gross Motor Function Classification System levels IV and V.


botulinum toxin A; cerebral palsy; children; hypertonia treatment; outcome

Is their a link between autism and lyme disease? No.

Some patients have asked about a link between autism and lyme disease. There does not appear to be a significant link. - JR


Correlation Debunked

Researchers find zero evidence for Lyme-induced autism.


The hypothesized link between autism and Lyme disease loses ground with a new study that found no evidence of an infection in patients with the social development disorder. The results, published today (April 30) in the Journal of the American Medical Association, imply that antibiotics against the Lyme disease pathogen—a popular new strategy for autism—will not ameliorate most patients’ symptoms.

“The data don’t address whether a single case of autism was ever caused by Lyme disease, but it rules out the suggestion that it does so with any frequency,” said Armin Alaedini, an immunologist at Columbia University Medical Center in New York and an author on the study. “I think that for me, this is the end of looking into the link between autism and Lyme.”  

In recent years, some doctors have anecdotally noted that many of their autism patients have Lyme disease. Two small studies listed in a booklet from a 2007 meeting of the Lyme-Induced Autism Foundation, a Corona, California-based organization that advocates an “eclectic healing approach,” reported that 1 in 5 autistic patients had the tick-borne disease. Websites on the topic now put that number closer to 9 out of 10. These statistics, however, have not been peer-reviewed. Nonetheless, some doctors prescribe antibiotics to autistic children and say the therapy quells their symptoms.

To systematically assess the prevalence of Lyme disease among people with autism, Armin Alaedini, an immunologist at Columbia University Medical Center in New York, and his colleagues analyzed blood samples from 120 children and teens: 70 participants had autism, and 50 served as healthy controls. Alaedini looked for antibodies against the bacterium underlying Lyme, Borrelia burgdorferi, and found that not a single participant tested positive for the infection.

“This means that you wouldn’t see 20 percent of children with autism getting their disease from Lyme,” Alaedini said. He entered into the study objectively, he said, wanting to explore a correlation that had gained traction among doctors and the public. “Autism has become a hot topic, and a lot of people are publishing findings that are bogus but still alarm parents.”

M. Ajamian et al., “Serologic markers of Lyme disease in children with autism,” Journal of the American Medical Association, 309: 1771-72, 2013.

Wednesday, January 21, 2015

Does nocturnal sweating suggest sleep apnea?

Does nocturnal sweating suggest sleep apnea?

This was the question of
today about sweating in sleep...

In clinical context, nocturnal sweating can be a  sensitive sign of sleep apnea.  But, its not specific.

Sweating often improves with OSA treatment.



 1993 Aug;16(5):409-13.

Clinical symptoms associated with brief obstructive sleep apnea in normal infants.


Relatively little data exist concerning the manifestations of repeated obstructive sleep apnea in normal infants. A questionnaire concerning daytime and sleep habits was completed by the parents of 4,100 healthy infants before they underwent a 9-hour night monitoring study. One hundred infants with an obstructive apnea index above 1.2 were randomly selected. They formed the "apnea" group. From the initial population, 300 infants with noapnea were also selected to form the "no-apnea" group. Both groups were matched for sex, gestational age, post conceptional age, birth weight, mother's age, parity and a family history of sudden infant death. Five variables from the questionnaires significantly differentiated the two groups of infants. When awake, the infants with apnea were characterized by a greater frequency of breathholding spells (22% of apnea infants) and episodes of fatigue during feeding (28%) than the non-apnea infants. During sleep, they exhibited a greater frequency of profuse sweating (15%), snoring (26%) or noisy breathing (44%). Multiple symptoms were present in some infants. A stepwise logistic regression resulted in two significant independent variables: profuse sweating during sleep (p = 0.008) and noisy breathing (p = 0.002). The predictive value of these two symptoms was tested on a new group of 650 healthy infants. The two independent variables led to the correct classification of 60 of the 67 infants with apnea (89.67%) and 382 of the 583 non-apnea infants (65.5%). A positive history alone had a positive predictive value of 0.21.(ABSTRACT TRUNCATED AT 250 WORDS)
[PubMed - indexed for MEDLINE]


 2012 May;97(5):470-3. doi: 10.1136/adc.2010.199638. Epub 2011 Mar 22.

Night sweats in children: prevalence and associated factors.



The authors aimed to examine the prevalence and factors associated with night sweats (NS) in primary school children.


Cross-sectional design.


Among 6381 children (median age 9.2 (7.7-10.7) years) with complete information on NS, 3225 were boys (50.5%). 747 children (11.7%) were reported to have weekly NS in the past 12 months. Boys were more likely than girls to have NS (p<0 .0001="" children="" class="highlight" have="" likely="" more="" nbsp="" ns="" span="" to="" were="" with="">sleep
-related symptoms and respiratory and atopic diseases. In addition, they were more likely to be hyperactive and have frequent temper outbursts. Using an ordinal regression model, NS was found to be significantly associated with male gender, younger age, allergic rhinitis, tonsillitis and symptoms suggestive of obstructive sleep apnoea, insomnia and parasomnia.


NS is prevalent among school-aged children and is associated with the presence of sleep-related symptoms and respiratory and atopic diseases.

  • Respiratory medicine

Nocturnal sweating—a common symptom of obstructive sleep apnoea: the Icelandic sleep apnoea cohort

  1. Thorarinn Gislason1,2
+Author Affiliations
  1. 1Department of Respiratory Medicine and Sleep, Landspitali—The National University Hospital of Iceland, Reykjavik, Iceland
  2. 2Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland
  3. 3Department of Medical Sciences: Respiratory Medicine and Allergology, Uppsala Universitet, Uppsala, Sweden
  4. 4Department of Otolaryngology, Landspitali—The National University Hospital of Iceland, Reykjavik, Iceland
  5. 5Division of Sleep Medicine/Department of Medicine, Center for Sleep and Circadian Neurobiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
  6. 6Department of Medicine, Philadelphia Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA
  1. Correspondence toDr Thorarinn Gislason;
  • Received 26 February 2013
  • Accepted 10 April 2013
  • Published 14 May 2013


Objectives To estimate the prevalence and characteristics of frequent nocturnal sweating in obstructive sleep apnoea (OSA) patients compared with the general population and evaluate the possible changes with positive airway pressure (PAP) treatment. Nocturnal sweating can be very bothersome to the patient and bed partner.
Design Case–control and longitudinal cohort study.
Setting Landspitali—The National University Hospital, Iceland.
Participants The Icelandic Sleep Apnea Cohort consisted of 822 untreated patients with OSA, referred for treatment with PAP. Of these, 700 patients were also assessed at a 2-year follow-up. The control group consisted of 703 randomly selected subjects from the general population.
Intervention PAP therapy in the OSA cohort.
Main outcome measures Subjective reporting of nocturnal sweating on a frequency scale of 1–5: (1) never or very seldom, (2) less than once a week, (3) once to twice a week, (4) 3–5 times a week and (5) every night or almost every night. Full PAP treatment was defined objectively as the use for ≥4 h/day and ≥5 days/week.
Results Frequent nocturnal sweating (≥3× a week) was reported by 30.6% of male and 33.3% of female OSA patients compared with 9.3% of men and 12.4% of women in the general population (p<0 .001="" 11.5="" 33.2="" adjustment="" after="" age="" and="" cardiovascular="" change="" compared="" decreased="" demographic="" difference="" disease="" factors.="" for="" frequent="" from="" full="" hypertension="" in="" insomnia="" nocturnal="" non-users="" of="" p="" pap="" prevalence="" related="" remained="" significant="" sleepiness="" sweating="" symptoms.="" the="" this="" to="" treatment="" was="" with="" younger="">
Conclusions The prevalence of frequent nocturnal sweating was threefold higher in untreated OSA patients than in the general population and decreased to general population levels with successful PAP therapy. Practitioners should consider the possibility of OSA in their patients who complain of nocturnal sweating.

Article summary

Article focus

  • Previous studies have suggested a possible relationship between obstructive sleep apnoea and frequent nocturnal sweating. However until now, studies comparing the prevalence of frequent nocturnal sweating in untreated sleep apnoea patients compared with the general population as well as changes with sleep apnoea treatment have been lacking. Our study focuses on the role of nocturnal sweating in sleep apnoea.

Key messages

  • Our study indicates a possible role of frequent nocturnal sweating as a marker for untreated sleep apnoea. One-third of adults with sleep apnoea experience this symptom and they are three times more likely to report it compared with adults in the general population. The symptom is responsive to treatment in the majority of sleep apnoea patients.
  • Clinicians should include sleep apnoea in the differential diagnosis of patients presenting with a complaint of nocturnal sweating and further investigate that possibility.

Strengths and limitations of this study

  • The strengths of this study include the detailed assessment of a large number of sleep apnea patients studied with a two year follow-up and the comparison with a general population cohort.
  • Our study was an observational study, not a randomised controlled trial, which may be considered a limitation. Other limitations include the use of subjective measures of sweating and the smaller number of women with sleep apnea than men, due to lower prevalence.