1. Neurological Disorders and Sleep:
A Case based discussion
Dr Pramod Krishnan
Consultant Neurologist and Epileptologist
Sleep Medicine Specialist
Manipal Hospital, Bengaluru
2. Introduction
• Since sleep is a complex brain-generated behaviour, it is expected
that diseases of the brain are frequently associated with sleep
disturbances.
• Sleep disorders can aggravate the neurological illness and can add
to the disability and poor quality of life.
• Sleep disorders in neurologic diseases is under-reported and
underdiagnosed.
• Sleep assessment and management should be part of the
treatment plan for all patients with neurological illness.
3. 1. Sleep and Epilepsy
• Sleep and Epilepsy share a bidirectional relationship.
• Sleep is affected by poorly controlled epilepsy, and epilepsy is
aggravated by poor sleep.
4. Effect of Sleep on Epilepsy
• Sleep deprivation (or oversleeping) can increase the risk of
seizures in a patient with epilepsy.
• In Epilepsy monitoring units, sleep deprivation is used to provoke
seizures for presurgical evaluation.
• Sleep EEG is often used to diagnose and classify epilepsy.
• Awake EEG is abnormal in 30% of patients with epilepsy.
• Combined awake and sleep EEG is abnormal in 80% of patients.
5. Epileptic syndromes associated with Sleep
• Continuous spike & waves during slow wave sleep (CSWS)
• Benign occipital epilepsy in infancy
• Lennox Gastaut Syndrome (LGS)
• Benign rolandic epilepsy (BECTS)
• AD Nocturnal Frontal Lobe Epilepsy (ADFLE)
• Epilepsy with GTCS on awakening
• Juvenile myoclonic epilepsy (JME)
6. Sleep and Epilepsy
• Seizures and interictal epileptiform discharges (IED)s are more
likely in non-REM sleep, whereas REM sleep is protective.
• Therefore, loss of REM sleep may enhance the kindling process
and cause progression in intractability of focal-onset seizures.
• Some seizures occur only in sleep, especially in non-REM sleep.
• Some epilepsies are more during the sleep- wake transition: e.g.
JME.
7. Case 1:
• 18/M, normal birth and development.
• GTCS since 16 years of age, 2 episodes. One episode occurred
early morning after a late night family function.
• Another episode occurred during his exams.
• Reports myoclonus since age of 14 years, whenever he gets up too
early, sleeps late or when sleep is interrupted.
• Has noted that missing AEDs may not trigger seizure, but missing
sleep does.
• Awake EEG was normal.
8. EEG shows frontally dominant generalised spike and wave discharges in sleep. This pattern is highly
suggestive of a genetic generalised epilepsy like Juvenile Myoclonic Epilepsy. Adequate sleep is a more
powerful therapy than AEDs. Patient needs to be counselled accordingly.
9.
10. Results
• In the JME group, sleep efficacy was reduced (p = <0.035)
• Increased sleep onset latency (p = 0.04)
• Reduced N2 sleep percentage (p = 0.005)
• Reduced NREM (non-rapid eye movement) sleep (p = 0.001)
• Increased mean wake percentage (p = 0.001).
• The frequency of arousals, involuntary limb movements, and event
related arousals in the JME groups was not different from the
controls.
11. Case 2
• 24/F, with multiple febrile seizures till 5 years of age.
• Has complex partial seizures since age of 14 years. Semiology
suggests temporal lobe origin, but lateralisation is unclear.
• Refractory to multiple AED trials.
• Admitted for presurgical evaluation.
• MRI brain: left sided mesial temporal sclerosis.
• Planned for surgery if Video EEG data is concordant.
12. EEG shows few left anterior temporal spikes during the awake EEG.
13. EEG in sleep shows left temporal intermittent rhythmic delta wave activity (TIRDA) highly suggestive of
epileptogenicity.
14. EEG in sleep shows independent right and anterior temporal epileptiform discharges, complicating the
plans for surgery.
15. Case 3:
• 7/M, perinatal insult, delayed developmental milestones.
• Infantile spasms at 5 months of age.
• Multiple seizure types since 2 years of age.
• On 4 anti-epileptic drugs.
• Seizure frequency has reduced but child is lethargic, has learning
disability.
• Plan to reduce AEDs if seizure control is adequate.
• Awake EEG shows a few spikes.
16. Awake EEG shows infrequent right and left fronto-central spikes.
17. Sleep EEG of the same patient shows frequent generalised epileptiform discharges.
18. Why are seizures and IEDs more common in
non-REM sleep?
• More neurons are in the resting state in non-REM sleep and thus
are available for recruitment into the epileptic network.
• However, during REM sleep, (like in awake state), overall greater
neuronal firing occurs, and neurons are less available to be
recruited into the interictal firing network.
19. Case 4:
• 7 year old boy with normal birth and development.
• Few seizures between 3-6 years of age. Well controlled with AEDs.
• Since 1 year, has progressive language regression, to a state of
almost being completely mute.
• He seems to not appreciate verbal commands and familiar sounds,
but responds to gestures and visual commands.
• MRI brain is unremarkable.
• Awake EEG showed infrequent generalised spikes.
20. Awake
Sleep
Initial awake EEG shows generalized spike and wave discharges. The second half of the trace shows sleep
EEG which shows continuous generalized spike and wave discharges.
21. Sleep EEG shows continuous generalized spike and wave discharges around 1.5–2 Hz, which during
non-REM sleep become generalized: a picture of electrical status epilepticus in sleep (ESWS)
23. Effect of Epilepsy on Sleep
• 2/3rd of patients with epilepsy have sleep disturbances.
1. Seizures are noted to cause postictal somnolence.
2. They can cause more wake after sleep onset.
3. Sleep fragmentation and daytime sleepiness.
4. REM sleep suppression during the sleep period following the
seizure.
5. Epilepsy patients have a higher prevalence of OSA.
6. Night time IEDs/ seizures can affect daytime learning.
24. Effect of Epilepsy on Sleep
• Better seizure control improves sleep quality and has beneficial
effect on learning, cognition and overall daytime performance.
• Most AEDs have a soporific effect, whereas some AEDs cause
insomnia: eg: Lamotrigine, Zonisamide.
• Chronopharmacology: adjusting so that sedating medications have
higher doses at night, may improve seizure response and lower
incidence of side effects.
25. 2. Sleep and Headaches
• Headaches and Sleep share a bidirectional relationship.
• Sleep disruption can predispose, provoke, and perpetuate
headaches, whereas good sleep improves headaches.
• In general, sleep deprivation and excessive sleep increase
headaches in both children and adults.
26. Case 5: Sleep and Migraine
• 41/F with 20 years of migraine. Initially episodic headaches.
• Daily headaches since 1 year: chronic migraine.
• Chronic insomnia: delayed sleep onset, maintenance.
• Significant life stressors.
• Partial benefit with medicines.
• Investigations normal.
27. Sleep and Migraine
• 86% of patients with episodic migraine have poor sleep quality.
• Poor sleep was associated with increasing headache frequency and
headache-related disability.
• Poor sleep hygiene can lead to transformed migraine, and
improvement of sleep-promoting behaviours can revert the
transformed migraine back to episodic migraine.
• Psychiatric consultation, improvement of sleep, yoga and
meditation improved sleep quality and improved migraine to a few
episodes in a month.
28. Sleep and headache
• Patients with insomnia have a 50% greater likelihood of having
headaches and more severe headaches.
• Bed partners of habitual snorers are more likely to have
headaches, suggesting the environmental disturbance of sleep
makes headaches more likely.
• 15%- 60% of patients with OSA report headaches, and these
individuals are more likely to develop morning headache,
migraine, chronic headache, and tension-type headaches.
• Treatment of OSA improves headache.
29. Headaches in Sleep
Headache type Sleep association Treatment
Cluster headache May occur near REM sleep Oxygen, triptans, verapamil,
valproate, Lithium.
Hypnic headache Awaken patient suddenly from sleep at
similar time each night, typically at 1:00
AM to 3:00 AM
Caffeine, lithium
Paroxysmal
hemicrania
Can occur out of sleep and last 2-45
minutes
Indomethacin
Sleep apnea headache Present upon awakening, resolves in
approximately 30 minutes.
Positive airway pressure
Migraine Migraine that occurs in sleep
(uncommon) usually occur with vivid
dreams suggestive of REM sleep.
TCAs, propranolol,
topiramate, valproate.
30. 3. Sleep and Alzheimers Dementia
• Sleep-wake and circadian disturbances start early in AD and
increase in prevalence and severity as AD progresses.
• Even at the earliest presymptomatic stage of AD, a bidirectional
association exists between sleep disturbance and AD pathology.
• Sleep-wake disturbances bothersome to caregivers are present in
approximately 40% of patients with AD.
• While typically a circadian phase advance occurs with aging, AD is
associated with a circadian phase delay. This probably causes
‘sundowning’.
31. Case 5
• 65/M, DM 2, HTN.
• Progressive cognitive decline since 3 years. Diagnosed as AD.
• Patient has delayed sleep onset, visual hallucinations, tries to get
out of bed, has fallen near the toilet. Frequent awakening.
• Agitation, crying and shouting during the night.
• Lethargic during the day, withdrawn. Not keen on any activities.
• Sleeps for 1-2 hours every few hours during the day.
• Marked care giver burden and sleep deprivation.
• Quitipine resulted in prolonged drowsiness needed admission.
32. Sleep and Alzheimers Dementia
• Insomnia at night may lead to wandering and subsequent risk of
falls or injury.
• Patients with AD may have excessive daytime sleepiness,
preventing engagement in social events and therapies, while
increasing the risk of accidents.
• Typical hypnotic medications for insomnia may increase the risk
of falls and injuries and should be used judiciously.
33. OSA and Alzheimers Dementia
• OSA is particularly common in AD, is present in 40% of patients
with AD, and in 70% of those in the institutionalized setting. It
may contribute to cognitive symptoms.
• Treatment of OSA may be helpful in ameliorating cognitive
decline in AD.
• Symptoms such as snoring, daytime sleepiness, or witnessed
apneas should prompt evaluation for OSA.
34. 4. Sleep and Parkinsons Disease (PD)
• All categories of sleep disorders affect patients with PD
throughout the course of their illness.
• Insomnia is the most common sleep disorder in PD.
• Sleep maintenance insomnia (sleep fragmentation) is the most
common type (seen in 80% patients).
• Parkinson Disease Sleep Scale and the Scales for Outcomes in PD
Sleep Scale (SCOPA-S) scale are two commonly used scales.
• A thorough review of medications is required.
35. Case 6:
• 69/M, with PD, presented with prominent fatigue, daytime
sleepiness and frequent awakening at night with poor sleep.
• There was no delay in sleep onset, no snoring or apneas.
• There is increased frequency of micturition at night.
• He was on Syndopa 6 tablets /day and Amantadine TID.
• He reported difficulties with turning in bed because of stiffness.
• He also had vague lower limb discomfort and leg cramps.
• Wife reported him to be withdrawn and with a low mood.
36. Causes of Sleep fragmentation in PD
Overnight emergence of PD motor symptoms.
Effect of dopaminergic medications
Sleep related movement disorders
Coexistent psychiatric symptoms, especially hallucinations.
Autonomic dysfunction and urinary disturbances
PD neurodegenerative process can affect sleep- wake centres.
37. Excessive daytime sleepiness (EDS) and PD
• EDS affects 50% of PD patients.
• Male gender, duration, and
severity of PD are risk factors.
• EDS in PD is associated with the
unexpected sudden onset of
sleep, or ‘‘sleep attacks,’’ that
pose safety implications, as ‘sleep
attacks’ at the wheel have been
reported in 23% of PD patients.
Etiology of EDS
Sleep fragmentation
PD neurodegenerative process
Age related changes in sleep
architecture
Dopaminergic medications, especially
the total dose
Loss of hypocretin/ orexin
38. Treatment of EDS in PD
• Healthy sleep hygiene
• Diagnosis and treatment of a coexistent sleep disorder.
• Soporific medications should be minimized, especially
dopaminergic agents.
• Medicines with activating properties (eg, selegiline or amantadine)
should be given earlier in the day.
• Stimulants like Modafinil 100-200 mg/day can be tried.
• Melatonin can improve sleep quality and reduce EDS.
39. Sleep disordered breathing and PD
• Prevalence of sleep disordered breathing is PD is same as that in
general population.
• OSA, CSA and mixed apneas may be equally represented in PD.
• Obesity, is not predictive of OSA in PD.
• The severity of sleep-disordered breathing and mean overnight
oxygen saturation levels correlate with PD severity.
• Nasal positive airway pressure (nPAP) is the preferred treatment.
• Adaptive servo-ventilation is the preferred type of PAP in patients
with PD with predominant central apneas.
40. Case 7
• 62/M, diagnosed as Idiopathic PD.
• Review of history revealed atypical features: symmetric onset of
rigidity, bradykinesia; no tremors; rapid progression; unsteadiness
and postural giddiness; autonomic disturbances.
• H/o talking in sleep and acting out dreams since the age of 40-45
years. Wife sleeps in another room because of violent movements.
• H/o chronic constipation and sexual dysfunction.
• Episodes of noisy breathing and choking in sleep.
41. RBD and PD
• RBD is present in approximately
30-50% of patients with PD.
• Precedes PD by several years.
• RBD predicts greater cognitive
decline in PD.
• Phenoconversion rates of
idiopathic RBD to PD is
approximately 75% to 90% of
patients 10 to 14 years following
RBD diagnosis.
Risk factors for RBD in PD
Akinetic/ rigid phenotype
Patients who experience falls
Higher disease severity
Greater motor fluctuations
Increased levodopa dose
Treatment: Melatonin, Clonazepam
42. RLS and PD
• RLS appears to be more common in PD than in the general
population and affects approximately 20% of patients with PD.
• Greater severity of PD, coexistent depression, and reduced serum
iron binding capacity are risk factors for RLS in PD.
• Diagnosis may be challenging since several symptoms of PD, such
as akathisia, overnight motor symptoms, and dystonic symptoms,
may mimic RLS.
• Treatment: dopaminergic agents, clonazepam, iron
supplementation.
43. 5. Sleep and Neuromuscular disorders
• Sleep disorders are most commonly hypoventilation due to
restrictive thoracic disease from respiratory muscle weakness.
Neuromuscular disorder Sleep comorbidity Comments
Amyotrophic lateral sclerosis Hypoventilation, obstructive
sleep apnea
Noninvasive ventilation improves
survival and quality of life
Myasthenia gravis Obstructive sleep apnea Consider nasal continuous positive
airway pressure therapy, alternative
measures (position restriction,
dental appliance, nasal expiratory
positive airway pressure device)
Restless legs syndrome Consider iron replacement therapy;
dopamine agonist, gabapentin
enacarbil, or pregabalin
44. Case 8:
• 56/M, with ALS, confined to wheelchair, with bulbar weakness.
• On home oxygen therapy in view of hypoxemia on oximetry.
• Reports EDS, frequent night-time awakening, but no h/o snoring.
• Epsworth Sleepiness scale of 14.
• PFT revealed a restrictive defect with FVC of 58% predicted, and
arterial blood gas on room air showed severe hypercapnia with pH
7.40, PCO2 67 mm Hg, and PO2 59 mm Hg.
• PSG showed severe OSA with an AHI of 38 events/hr of sleep.
45. PSG shows OSA. Despite thoracic and abdominal efforts, there is a cessation of airflow.
46. Sleep and Amyotropic Lateral Sclerosis
• Hypoventilation due to restrictive thoracic disease in ALS often
presents as orthopnea at night, prior to daytime respiratory
symptoms.
• Morning headaches, daytime sleepiness and cognitive dysfunction
are also common symptoms of hypoventilation.
• Because of weakness of oropharyngeal musculature, patients with
ALS are at high risk of OSA.
• Central apneas, RLS, muscle cramps, discomfort from immobility,
depression, and ALS-associated dementia can affect sleep.
47. Screening for hypoventilation
• FVC in supine and upright position.
• Nocturnal desaturation with SaO2 < 90% for > 1 min is more
sensitive for hypoventilation than FVC.
• PSG with transcutaneous PCO2 monitoring (in which PCO2
increases more than 10 mm Hg during sleep).
48. Treatment of hypoventilation in ALS
• The most effective treatment is nocturnal ventilation.
• Both invasive (via tracheostomy) and NIV are available.
• NIV prolongs survival by 7 to 12 months, (longer than riluzole).
• NIV should be offered, ‘‘at the earliest sign of nocturnal
hypoventilation or respiratory insufficiency.’’
• Volume-targeted ventilation modes are preferred in ALS.
• In comorbid OSA, PSG for NIV titration is recommended to
identify settings optimal for treating hypoventilation and OSA.
49. Sleep and Muscle disease
Muscle disease Sleep Comorbidity Comments
Duchennes muscular
dystrophy
Hypoventilation Both fixed restrictive and functional
restrictive defects, often require
tracheostomy because of
24 hour/d ventilation
Myotonic dystrophy Obstructive sleep apnea,
central sleep apnea,
hypersomnia
Frequent central apneas in response
to positive airway pressure treatment,
low hypocretin/orexin levels in CSF
Inflammatory myopathies Obstructive sleep apnea,
hypoventilation
Frequently asymptomatic, so screening
is essential; dermatomyositis most
commonly affected; hypoventilation is
related to diaphragmatic weakness
50. Sleep and Neuropathy
Neuropathy Sleep comorbidity Comments
Acute inflammatory
demyelinating
polyradiculoneuropathy
(Guillain-Barre´ syndrome)
Hypoventilation, REM
sleep behaviour disorder
May require intubation in
acute phase; REM sleep
behaviour disorder and other
narcolepsy like symptoms may
be related to low orexin levels
in CSF.
Charcot-Marie-Tooth disease Restless legs syndrome Treatment strategy same as
idiopathic restless legs
syndrome
51. Conclusion
• Sleep disorders are widely prevalent in most neurological
disorders, especially, neurodegenerative ones.
• The relationship between sleep and neurological disorders is
usually bidirectional .
• They are under-reported and under-diagnosed.
• They result in increased disability and quality of life.
• They affect treatment decisions, choice of medications.
• Improving sleep quality parameters improves the outcomes of the
neurological disorder.
