REM Related parasomnias

Clinic

• RBD = Rapid eye movement sleep Behavior Disorder = REM behavior disorder = REM Related parasomnias
• RBD in brief: Normal REM sleep Muscle atonia is absent + Dreamer acting out their dreams, with complex behaviors.
• It is a sleep disorder in which people act out their dreams / Abnormal behavior during REM sleep.
• Loss of motor inhibition leads to sleep behaviors ranging from simple limb twitches to more complex integrated movements
• RBD is a very strong predictor of progression to a synucleinopathya and may begin years or decades before the onset of Parkinson's disease /dementia with Lewy bodies).
• Melatonin is useful in the treatment of RBD

Characteristics

• RBD characterized by purposeful movements during REM sleep with or without vocalization linked to a dream.
• Symptoms are usually associated with enacting Undesirable / Violent dreams where the patient is Attacked, /Chased /Compromised. He often wakes up abruptly with prompt alertness and can recount the dream coherently. The eyes are typically closed during an event, and he would not normally interact with the environment but rather only behave with the dream.
• Increased periodic limb movement may occur that may disrupt the sleeping partner.
• The sleeping person may be unaware of these movements.
• Dreams often involve violent or aggressive actions, and an attack theme like being chased by people or animals.

Sign / Symptoms

Sleep symptoms

• Complex behavior such as Walking out of bed / Falling / Screaming / Shouting / Laughing / Crying / Arm flailing / Kicking / Punching / Choking / Jumping out of bed in response to action-filled or violent dreams, such as being chased or defending yourself from an attack
• Other sleep behaviors including stereotypical hand motions, reaching gestures, and punching or kicking.

• Vocalization /Screaming/ Swearing / Talking Laughing Shouting /Emotional outcries or Even cursing that may be associated with dreams
• Motor activity, simple or complex, that may result in injury to patient or bed-partner
• Being able to recall the dream if you awaken during the episode

Other symptoms

Non-Motor Abnormalities

• Mild cognitive impairment
• Impairments in color vision
• Autonomic dysfunction (Orthostatic hypotension, Constipation, Urinary problems and Sexual dysfunction)
• Depression
• Loss of olfaction

Motor Abnormalities in iRBD

Roughly 34% of people with iRBD present with subtle extrapyramidal motor signs include

• Bradykinesia
• Functional deficits
• Facial and speech abnormalities
• Gait and postural impairment
• Rigidity
• Tremor

Para clinic findings

• Subtle cortical EEG slowing
• Reduced cardiac ¹²³I-Metaiodobenzylguanidine scintigraphy
• Decreased dopamine transporter imaging
• Increased substantia nigra echogenicity

Cause

• RBD is precipitated by aberrant connections between the brain-stem control of muscle tonicity and cerebral cortex.
• RBD is also associations with
  • Traumatic brain injury (TBI)
  • Post-traumatic stress syndrome (PTSD)
  • Congenital and neurodevelopmental disorders

Related disease

• Dementia with Lewy bodies
• Parkinson's disease
• MSA = Shy-Drager syndrome = Olivopontocerebellar atrophy = Striatonigral degeneration
• Ataxia or chorea
• Dysarthria
• Dysphagia
• Narcolepsy
• Guillain–Barré syndrome
• Limbic encephalitis
• Morvan's syndrome / Agrypnia excitata
• MS

• Seizures including Benign childhood epilepsy, Complex partial seizures, Epilepsia partialis continua, Epileptic encephalopathy, Juvenile myoclonic epilepsy, Psychogenic nonepileptic seizure
• Confusional arousals
• Delirium
• Obstructive sleep apnea (OSA)
• Parasomnia overlap syndrome
• Periodic limb movement disorder
• PTSD
• Sleep terror

Pathophysiology

• A prime feature of RBD is the intermittent loss of atonia during REM sleep, which leads to dreaming-related motor behaviors.
• Muscle atonia during normal REM sleep is controlled within the pontine tegmentum and medial medulla.
  • Interruption or disinhibition of these brain-stem areas is the pathophysiology of RBD.
  • Brainstem circuits (Pontomedullary brainstem) that control atonia during REM sleep may be damaged,.
• Excitatory glutamatergic neurons within the dorsal pre-coeruleus nucleus activate the spinal cord inhibitory interneurons, thereby initiating REM sleep atonia.
• RBD is associated with autoimmune encephalitis.
• A novel association between antibodies (mainly IgG4) to a neuronal antigen against IgLON5 and RBD has been reported suggesting a tauopathy.
• Neuronal loss / Tau deposits in tegmentum of the brain-stem and hypothalamus (Autoimmune-mediated RBD)
• The pathogenesis of RBD is distinct in cases of narcolepsy as it is linked to orexin deficiency. In contrast to idiopathic RBD, in cases of RBD-narcolepsy combination, alpha-synuclein biomarkers are usually not detected.
• REM sleep circuits are located in caudal brainstem structures—the same structures that are known to lead to be implicated in the synucleinopathies.
• Motor deficits like those seen in RBD are known to result from lesions in those circuits.

Classification

Idiopathic RBD

IRBD manifests as unpleasant dreams and vigorous behaviours during REM sleep that can result in injuries. They have no known neurological diseases or motor or cognitive complaints; however, this sleep disorder is not harmless. In most cases, IRBD is the prelude of the synucleinopathies Parkinson's disease, dementia with Lewy bodies, or, less frequently, multiple system atrophy. Patients can show abnormalities that are characteristic of the synucleinopathies, and longitudinal follow-up shows that most patients develop parkinsonism and cognitive impairments with time. Thus, diagnosis of IRBD needs to be accurate and involves informing the patient of the risk of developing a neurodegenerative disease.

In iRBD no evidence of neurological disease is found, however, in many iRBD patients subclinical abnormalities have been detected such as

• Olfactory deficits
• Cognitive dysfunction
• Impaired color vision
• Dysautonomic abnormalities

Among these disorders RBD is distinctly more prevalent in MSA, maybe because brain-stem cell loss is widespread and severe in this disorder.

• Retrospective assessment indicates that RBD frequently precedes the onset of these disorders but this seems to be most pronounced in DLB probably reflecting the differences in clinical course and progression in these disorders.
• RBD has also been observed in tauopathies and disorders with a neuroimmunological background, however, at the moment the association with synucleinopathies outweighs that with any other.
• Follow-up of patients with iRBD shows an increased risk for developing neurodegenerative diseases that strongly depends on the length of the follow-up period. Recent evidence suggests that iRBD is an early sign of a slowly evolving neurodegenerative disorder or a long-term predictor of it. In the following this evidence will be summarized and presented focusing on the prevalence and features of RBD in neurodegenerative disorders, the emergence of neurodegenerative disorders in long-term follow-up studies of patients with iRBD and baseline differences between iRBD patients who developed a neurodegenerative disease and those who remained disease free.

Symptomatic RBD

When it results from an identifiable causes such as

1. RBD-narcolepsy combination
2. Autoimmune-mediated RBD

Morvan syndrome and limbic encephalitis, associated with voltage-gated potassium channel-complex antibodies, principally against CASPR2 and LGI1, can result in profound insomnia and RBD.

Patients with aquaporin-4 antibodies and neuromyelitis optica may develop narcolepsy in association with other evidence of hypothalamic dysfunction, sometimes as the initial presentation.

Central sleep apnea and central neurogenic hypoventilation are found in patients with anti-N-methyl-d-aspartate receptor antibody encephalitis, and obstructive sleep apnea, stridor, and hypoventilation are prominent features of a novel tauopathy associated with IgLON5 antibodies.

In addition, paraneoplastic diseases may involve the hypothalamus and cause sleep disorders, particularly narcolepsy and RBD in those with Ma1 and Ma2 antibodies. Patients with antineuronal nuclear autoantibodies type 2 may develop stridor.

Several lines of evidence suggest that narcolepsy is an autoimmune disorder. There is a strong relationship with the human leukocyte antigen (HLA) DQB1*06:02 haplotype and polymorphisms in the T-cell receptor alpha locus and purinergic receptor P2Y11 genes. Patients with recent-onset narcolepsy may have high titers of antistreptococcal or other antibodies, although none has yet been shown to be disease-specific but, supporting an immune basis, recent evidence indicates that narcolepsy in children can be precipitated by one type of vaccination against the 2009-2010 H1N1 influenza pandemic.

REM sleep without atonia (RSWA)

Loss of normal muscle atonia during rapid eye movement sleep, measured via electromyography.

Miasmatic analysis

• Delirium is the best main rubric, since in RBD, the patient acts according to his dreams. Is it a dellirius state? Of course. Now we have a good structure but in order to specify a distinct miasm and effective miasmatic remedy, I decide to categorize RBD including
  1. Autonomic dysregulation RBD: According to recent researches, only Pure Autonomic Failure is important in RBD and Parkinson.The most important symptom of PAF is Orthostatic Hypotention. By this rubric HSV-1 would be the only miasm of this branch of RBD.
  2. Narcolepsy: Here there is good miasmatic situation. Recent researches bring up autoimmune foundation when Narcolepsy paired with cataplexy. Intrestingly cataplexy is known with its sudden loss of muscle strength, which is the main character of Sleep paralysis and RBD. If you do not catch the point till now, there is no way for explaining such a strong complex relationship between Narcolepsy, Cataplexy, RBD, autoimune disorders. This would be a prion miasms named FFI.
  3. Nightmare disorder: TBE / RBS. The main core of nightmare is Fear and of course its occurance through REM sleep opposed to Sleep terror disorder which are NREM sleep disorders.
  4. Catathrenia / Sleep paralysis: RBS is the first and best miasm because it is Apnea and specially for making strange voice in his throat. The second miasm would be INFL since it cover Dellirium + Apnea.

	Idiopathic RBD	RBD-Narcolepsy Combination	Autoimmune-mediated RBD
Parkinsonism Cogwheel sign Rigidity Resting tremor	+++
Dementia
Cognitive impairments	+++
Gait abnormalities	+++		+++
Ataxia			+++
Dysarthria			+++
Dysphagia			+++
Autonomic dysfunction	+++
Olfactory deficits	+++
Impaired color vision	+++

Differential Diagnosis

• Non-REM parasomnias (sleepwalking, sleep terrors)
• Periodic limb movement disorder
• Severe obstructive sleep apnea
• Dissociative disorders

Related entities

• Medulla oblongata is one of sleep centers. It sends signals to relax muscles essential for body posture and limb movements, so that we don’t act out our dreams.
• We know Bulbar palsy, which refers to impairment function of the glossopharyngeal nerve (CN IX), the vagus nerve (CN X), the accessory nerve (CN XI), and the hypoglossal nerve (CN XII). Therefore bulbar palsy is possibly related to RBD. Recent studies documented this relation. The lost missing ring is IgLON5 antibodies.
  

RBD Entities / Miasms

RBD	FFI	TBE
Delirium	+++	+++
Cognition impaired	+++	+++
Ataxia	+++	+++
Autonomic Dysregulations	+++	+++
Orthostatic Hypotention		+++
Constipation	+++
Urine, Incontinence		+++
Male, impotence	+++
Depression	+++	+++
Dysarthria	+++
Ansomnia

Subtypes

Recurrent isolated sleep paralysis

• Recurrent isolated sleep paralysis is an inability to perform voluntary movements at sleep onset, or upon waking from sleep.
• Although the affected individual is conscious and recall is present, the person is not able to speak or move.
• However, respiration remains unimpaired.
• The episodes last seconds to minutes and diminish spontaneously.
• The lifetime prevalence is 7%.
• Sleep paralysis is associated with sleep-related hallucinations.
• Predisposing factors: Sleep deprivation, Irregular sleep-wake cycle
• A possible cause could be the prolongation of REM sleep muscle atonia upon awakening.

Nightmare disorder

• Nightmares are like dreams primarily associated with REM sleep.
• Nightmare disorder is defined as recurrent nightmares associated with awakening dysphoria that impairs sleep or daytime functioning.
• It is rare in children, however persists until adulthood.
• About 2/3 of the adult population report experiencing nightmares at least once in their life.

Catathrenia

• It consists of breath holding and expiratory groaning during sleep
• It is distinct from both somniloquy and obstructive sleep apnea.
• The sound is produced during exhalation as opposed to snoring which occurs during inhalation.
• It is usually not noticed by the person producing the sound but can be extremely disturbing to sleep partners, although once aware of it, they tend to be woken up by their own groaning as well.
• Bed partners generally report hearing the person take a deep breath, hold it, then slowly exhale; often with a high-pitched squeak or groaning sound.

Sleep-Related painful erections

• Painful erections appear only during REM sleep
• Sexual activity does not produce any pain.
• There is not any lesion or physical damage but an hypertonia of the pelvic floor could be one cause.
• It affects men of all ages but especially from the middle-age.