Parkinson’s disease (PD) is a neurodegenerative disorder that affects predominately dopamine-producing (“dopaminergic”) neurons in a specific area of the brain called substantia nigra.

Symptoms generally develop slowly over years. The progression of symptoms is often a bit different from one person to another due to the diversity of the disease. People with PD may experience:

• Tremor, mainly at rest and described as pill rolling tremor in hands. Other forms of tremor are possible
• Bradykinesia
• Limb rigidity
• Gait and balance problems

The cause remains largely unknown. Although there is no cure, treatment options vary and include medications and surgery. While Parkinson’s itself is not fatal, disease complications can be serious.

The first step to living well with Parkinson’s disease is to understand the disease and the progression:

It is possible to have a good to great quality of life with PD. Working with your doctor and following recommended therapies are essential in successfully treating symptoms by using dopaminergic medications.

People with PD need this medication because they have low levels or are missing dopamine in the brain, mainly due to impairment of neurons in the substantia nigra.

It is important to understand that people with PD first start experiencing symptoms later in the course of the disease because a significant amount of the substantia nigra neurons have already been lost or impaired. Lewy bodies (accumulation of abnormal alpha-synuclein) are found in substantia nigra neurons of PD patients.

Scientists are exploring ways to identify biomarkers for PD that can lead to earlier diagnosis and more tailored treatments to slow down the disease process. Currently, all therapies used for PD improve symptoms without slowing or halting the disease progression.

In addition to movement-related (“motor”) symptoms, Parkinson’s symptoms may be unrelated to movement (“non-motor”). People with PD are often more impacted by their non-motor symptoms than motor symptoms. Examples of non-motor symptoms include: apathy, depression, constipation, sleep behavior disorders, loss of sense of smell and cognitive impairment.

In idiopathic Parkinson’s disease, progression tends to be slow and variable. Doctors often use the Hoehn and Yahr scale to gauge the progression of the disease over the years. The scale was originally implemented in 1967 and it included stages zero to five, where zero is no signs of Parkinson’s and five is advanced PD. It was later changed to become the modified Hoehn and Yahr scale.

Scientists believe a combination of genetic and environmental factors are the cause of Parkinson’s disease (PD). PD is an extremely diverse disorder. While no two people experience Parkinson’s the same way, there are some commonalities. PD affects about ten million worldwide. The main finding in brains of people with PD is loss of dopaminergic neurons in the area of the brain known as the substantia nigra.

Parkinson’s disease (PD) is called a movement disorder because of the tremors, slowing and stiffening movements it can cause, and these are the most obvious symptoms of the disease. But Parkinson’s affects many systems in the body. Its symptoms are different from person to person and usually develop slowly over time.

There is no single test or scan for Parkinson’s, but there are three telltale symptoms that help doctors make a diagnosis:

1. Bradykinesia
2. Tremor
3. Rigidity

Bradykinesia plus either tremor or rigidity must be present for a PD diagnosis to be considered.

Another movement symptom, postural instability (trouble with balance and falls), is often mentioned, but it does not occur until later in the disease progression. In fact, problems with walking, balance and turning around early in the disease are likely a sign of an atypical parkinsonism.

• Cramping (dystonia): sustained or repetitive twisting or tightening of muscle.
• Drooling (sialorrhea): while not always viewed as a motor symptom, excessive saliva or drooling may result due to a decrease in normally automatic actions such as swallowing.
• Dyskinesia: involuntary, erratic writhing movements of the face, arms, legs or trunk.
• Festination: short, rapid steps taken during walking. May increase risk of falling and often seen in association with freezing.
• Freezing: gives the appearance of being stuck in place, especially when initiating a step, turning or navigating through doorways. Potentially serious problem as it may increase risk of falling.
• Masked face (hypomimia): results from the combination of bradykinesia and rigidity.
• Micrographia: small, untidy and cramped handwriting due to bradykinesia.
• Shuffling gait: accompanied by short steps and often a stooped posture.
• Soft speech (hypophonia): soft, sometimes hoarse, voice that can occur in PD.
  

Dopamine is a chemical messenger (neurotransmitter) that is primarily responsible for controlling movement, emotional responses and the ability to feel pleasure and pain. In people with Parkinson’s, the cells that make dopamine are impaired. As Parkinson’s progresses, more dopamine-producing brain cells die. Your brain eventually reaches a point where it stops producing dopamine in any significant amount. This causes increasing problems with movement.

There is no standard treatment for Parkinson’s disease (PD). Treatment for each person with Parkinson’s is based on his or her symptoms.

Treatments include medication and surgical therapy. Other treatments include lifestyle modifications, like getting more rest and exercise.

There are many medications available to treat the Parkinson’s symptoms, although none yet that reverse the effects of the disease. It is common for people with PD to take a variety of these medications — all at different doses and at different times of day — to manage symptoms.

While keeping track of medications can be a challenging task, understanding your medications and sticking to a schedule will provide the greatest benefit from the drugs and avoid unpleasant “off” periods due to missed doses.

Coronavirus disease 2019 (COVID-19) is a respiratory illness that can spread from person to person. Seniors are the most vulnerable. Since many people with Parkinson’s disease (PD) are above age 60, the our doctor is here to help you learn more about how COVID-19 affects people with Parkinson’s and urges you to get vaccinated to stay safe.

To reduce the risk of being infected with COVID-19 and its variants, and possibly spreading it to others, it is recommended to wearing a mask outdoors in public if you are in an area of substantial or high transmission. Fully vaccinated people who have been in contact with someone suspected or confirmed with COVID-19 should be tested three to five days after exposure.

Clinical Overview

Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures, or both. Dystonic movements are typically patterned, twisting, and may be tremulous. Dystonia is often initiated or worsened by voluntary action and associated with overflow muscle activation.

The physical sign of dystonia is identified by the observation of dystonic postures and movements and of conditions that specifically activate, increase or decrease this phenomenology. A typical example is when a tactile stimulus or a voluntary geste (known as a sensory trick or geste antagoniste), such as touching the affected or an adjacent body part, can reduce the dystonia. These features are observed in a variety of dystonia syndromes.

The neural mechanism underlying dystonia involves many regions of the central nervous system (particularly: the basal ganglia, cerebellum, supplementary motor areas and sensorimotor cortex) leading to impaired inhibition, abnormal plasticity and sensorimotor dysfunction. Different levels of functional impairment lead to varying degrees of observed clinical severity.

Clinical Overviews

Chorea

Chorea is an abnormal involuntary movement derived from the Greek word “dance”. It is characterized by brief, abrupt, irregular, unpredictable, non-stereotyped movements. In milder cases, chorea may appear purposeful. The patient often appears fidgety and clumsy. Overall, chorea can affect various body parts, and interfere with speech, swallowing, posture and gait, and disappears in sleep.

Huntington’s disease

Huntington’s disease is an autosomal dominant neurodegenerative disorder (therefore, each child of an affected parent has a 50% chance of developing the disease). It is caused by a cytosine-adenine-guanine (CAG) trinucleotide repeat expansion in the huntingtin (HTT) gene on chromosome 4p. Most people develop Huntington’s disease between 30-54 years old but it can manifest as early as 4 years old and as late as 80 years. The worldwide prevalence of HD is approximately 2.7 per 100,000.

Clinical Overview

Ataxia, defined as incoordination of voluntary muscle movement, is a neurological sign, not a disease. Ataxia can be the chief complaint or part of the presenting symptoms, and it is usually caused by cerebellar dysfunction, impaired vestibular or proprioceptive afferent input to the cerebellum. Patient with ataxia usually present with poor coordination, unsteady gait with a tendency to stumble, difficulty with fine motor tasks, impaired swallowing, and abnormalities in eye movements. Neurologists should be familiar with specific terms for ataxia and use them appropriately when communicating with colleagues. The following clinical terms are often used in describing ataxia, including sensory ataxia, limb ataxia, gait ataxia, titubation, dysdiadochokinesia, intention tremor, dysmetria, scanning speech, square-wave jerks/ocular flutter/opsoclonus and nystagmus. It is important to understand the nomenclature because it sometimes implies a certain ataxic disorder.

Ataxia may have an acute onset, especially those ataxias resulting from stroke, hemorrhage, or infection of the cerebellar and/or its afferent or efferent, which can have a rapid progression with catastrophic impact. It can also have an insidious onset with a chronic and slowly progressive clinical course (hereditary ataxia, eg, spinocerebellar ataxias [SCAs]). Some patients have a subacute onset, as due to certain medications, alcohol abuse or from immunologic (eg, paraneoplastic syndromes) or infectious disorders, which may just have a narrow therapeutic window. A prompt management strategy for treatable causes of ataxia should not be missed. Of course, ataxia can also be benign in symptomatic disorders (eg, vestibular neuritis).

Clinical Overview

Essential Tremor

Essential tremor (ET) is the most common tremor syndrome seen in adults. Essential tremor is an isolated tremor syndrome of bilateral upper limb action tremor with at least 3 years’ duration, as recently defined by the MDS Task Force for Tremor. Tremor in other locations (e.g., head, voice, or lower limbs) may (or may not) be present. But there are no other neurological signs, such as dystonia, ataxia, or parkinsonism. To further clarify and to delineate ET from other tremors, exclusion criteria were also formulated: Thus, isolated focal tremors (voice, head), orthostatic tremor with a frequency >12 Hz, task- and position-specific tremors and sudden onset and step-wise deterioration do not fall into the category of ET.

Tremor

Tremor is an involuntary, rhythmic, oscillatory movement of a body part. Tremor results from contractions of agonist and antagonist muscles entrained by a signal pattern originating from an oscillator in the central nervous system. Resting tremor occurs in a body part that is not activated and completely supported against gravity. Action tremor refers to tremor occurring with voluntary muscle contraction and is subdivided into postural tremor, isometric tremor and kinetic tremor. The latter is further subdivided into simple kinetic, intention tremor, and task specific tremor, such as writing tremor.

Clinical Overview

Myoclonus is characterized by sudden, brief, involuntary jerks of a muscle or group of muscles. It can be either a positive jerk caused by a muscular contraction, or a negative jerk caused by an interruption of muscle activity. The classification of myoclonus can be made anatomical, clinical or etiological; however, the anatomical origin of jerks is most commonly used in clinical practice. With help of electrophysiological examination using electromyography (EMG) in combination with electro-encephalography (EEG), the jerks can be subdivided in cortical – which is the most common –subcortical (or non-cortical) including brainstem, spinal, and peripheral myoclonus. The clinical presentation of myoclonus is of added value in the differentiation of these subtypes. Cortical myoclonus present mainly in distal limbs and the face are stimulus-sensitive, opposed to subcortical myoclonus showing mostly proximal and axial jerks.

A wide variety of both acquired and genetic causes are associated with myoclonus, making the diagnostic process of finding the etiology challenging. Both the anatomical substrate and the additional accompanying clinical features provide important information regarding the underlying disease and help guide towards a more specific differential diagnosis.

Acquired causes

In cortical and subcortical myoclonus, an acquired cause is common and characterized by an acute or subacute onset and/or fast progression of disease. Medication or toxic agents induced myoclonus should be considered first, especially if the jerky movements started more or less acutely at the start of treatment, because cessation or detoxification will ameliorate the symptoms. Subsequently, routine laboratory tests can detect etiologies such as homeostatic imbalance, organ failure and infections. Immune-mediated disorders (e.g. anti-NMDAR encephalitis, stiff person syndrome (SPS), opsoclonus-myoclonus syndromes (OMS)) become more likely one systemic signs of infection are present. Some of these disorders are treatable and, therefore, early recognition is critical. A brain MRI is a helpful next step in identifying the underlying disease, both acquired and genetic causes.

In spinal and peripheral myoclonus, signs of muscle denervation or structural lesions must be assessed with help of electrophysiological testing or imaging. Propriospinal myoclonus, closely resembling spinal myoclonus and characterized by generalized jerks of the trunk and abdominal muscles with a variable duration from 100 – 1000ms, is usually a functional movement disorder.

Genetic causes

Only cortical and subcortical myoclonus are associated with genetic disorders and in most cases next generation sequencing (NGS) is indicated after ruling out an acquired cause. However, keep in mind the mitochondrial disorders (e.g. MERRF) and neurodegenerative disorders (e.g. Alzheimer’s disease) for mitochondrial defects are not identified with NGS and in only a small percentage of neurodegenerative disorders the underlying defect is known.

Compared to an acquired cause, a genetically determined myoclonus syndrome is suspected in cases with an early onset and a slower progression of disease. In the majority of cases, one of two clinical syndromes is seen: cortical myoclonus in combination with ataxia (e.g. progressive myoclonus epilepsy / progressive myoclonus ataxia) or subcortical myoclonus in combination with dystonia. Almost all genetic disorders present with an additional movement disorder. Exceptions include familial cortical myoclonus with epilepsy (BAFME or FCMTE), some epileptic encephalopathies and hyperekplexia. Unfortunately, the majority of the genetic defects causing genetically determined myoclonus syndromes remain unknown.

Identifying the anatomical substrate is not only helpful in the diagnostic process, but also has consequences for the treatment strategy. Levetiracetam, valproic acid and clonazepam are generally considered to be the first choices of treatment in cortical myoclonus, whereas only clonazepam is the first choice in subcortical, spinal and peripheral myoclonus.

Startle is a stereotypical response to a sudden and unexpected stimulus. In most instances, the stimulus is acoustic, but other modalities such as tactile, visual, or vestibular are also effective stimuli. Exaggerated startle is a feature of various neurologic and psychiatric conditions. These startle syndromes are a diverse and heterogeneous group of syndromes enfolding three categories: hyperekplexia, stimulus-induced disorders and neuropsychiatric disorders.

Hyperekplexia is a rare genetic clinical syndrome that is characterized by brisk and generalized startle in response to (most often acoustic or tactile) stimulation. The medical triad includes 1) generalized stiffness at birth (slowly diminishing in the first year of life), 2) excessive startle reflexes and 3) short-lasting generalized stiffness following startle resulting in violent falls. The startle response originates from the brainstem and is treated with clonazepam. On examination, at all ages, there is an exaggerated head-retraction reflex. The most common gene affected concerns GLRA1, responsible for 80% of all hyperekplexia pedigrees.

Stimulus induced disorders show excessive responses due to a startling stimulus. These disorders are either non-epileptic (e.g. paroxysmal kinesigenic dyskinesias, episodic ataxia, cataplexy) or epileptic (e.g. reflex epilepsy) and usually start in childhood. The third group, the neuropsychiatric startle syndromes often develop later in life and include startle-induced tics, functional startle syndromes and anxiety disorders (e.g. posttraumatic stress syndrome), and the culture-specific syndromes such as Latah and the Jumping Frenchmen of Maine.

Clinical Overview

Tics are brief movements or sounds that resemble voluntary actions, but appear suddenly, without regularity, often exaggerated in intensity and are repetitive and inopportune to social context. Tics also lack behavioral flexibility, which is a characteristic marker for voluntary actions and defines normal human goal-directed behavior. Both motor and vocal (or phonic) tics can be highly variable within and between individuals and indeed any possible movement or sound can be a tic. Hence, among the spectrum of hyperkinetic movement disorders, tics have the widest phenomenological variability.

On grounds of phenomenology, tics are classified into simple motor (e.g. blinking, eye rolling) or vocal (simple sounds as “ah”, “uh” or grunts, coughs, throat clearing, hissing sounds etc.), when they involve specific effectors of one body part or present with isolated vocalizations. Complex tics refer to motor or vocal behaviors that appear patterned, as for example gestures (e.g. flailing both arms as if waving goodbye or clapping hands) or complete words or even sentences (e.g. ‘hello’, ‘mango salad’, ‘have a nice day’ etc.). Motor tic behaviors are most often clonic (i.e. brief, abrupt and rapidly occurring), but some tics may be tonic (i.e. isometric muscle tensing) or dystonic (leading to – somewhat – prolonged abnormal postures). The rubric of complex tic behaviors also encompasses three further phenomena: echo-, pali- and coprophenomena. Echophenomena denote the imitation of movements (echopraxia) or sounds (echolalia) from the surrounding environment, which often occur in the absence of explicit awareness. Paliphenomena refer to the repetition of actions (palipraxia) or sounds (palilalia).

Coprophenomena describe the occurrence of obscene gestures, including writing, or vocalizations that occur without intent.

Tics have two additional distinctive features. First, they are often preceded by an unpleasant sensory experience, most commonly labeled as “premonitory urge”. Akin to interoceptive experiences, patients typically have difficulties providing exact accounts of premonitory urges, often using terms as “itch”, “burning”, “muscle tension” or “the need to perform a tic” to describe them. Usually, the execution of a tic behavior provides temporary relief from the impeding premonitory urge. Second, tics can be voluntarily suppressed for brief periods of time. Indeed, both the presence of premonitory urges and the capacity to effortfully suppress tic behaviors on demand are helpful clues in severe cases, where the distinction from other hyperkinetic movement disorders, as for example, chorea may be difficult.

Tics can be encountered in a wide range of neurodevelopmental, neurometabolic and neurodegenerative disorders. However, in the clinical setting are most commonly seen in Gilles de la Tourette syndrome (or just Tourette syndrome: TS). According to DSM-5, TS is defined by the presence of at least two motor tic behaviors and one vocal tic behavior for a minimum period of a year, manifesting before the age of 18. Other primary tic disorders include chronic motor and vocal tic disorder – defined by the presence of either motor or vocal tics as isolated manifestations -, and provisional tic disorder, when tics have been present for less than a year. It is noteworthy, that in the majority of cases with TS, patients will also present with a wide range of neuropsychiatric comorbidities. These include attention-deficit hyperactivity disorder (ADHD), obsessive compulsive behavior/disorder (OCB/OCD), depression, anxiety disorder, self-injurious behavior and others. Importantly, the range of clinically relevant comorbidities in a given individual may change with time. For example, depression and anxiety disorders become more prominent in adults with TS, as opposed to young children, where ADHD might often be a core clinical issue.

As with any disorder, but more so with tics, treatment already begins at the time of diagnosis. This means that in the majority of cases explaining the neurobiological background of the disorder and the spectrum of associated phenomena and comorbidities might suffice. Moreover, in many cases a prioritization of treatment goals could point towards interventions aiming to reduce the impact of comorbidities such as ADHD, OCD or depression. However, when tics are harmful or socially disturbing, therapeutic venues, including behavioral and pharmacological are necessary. Within the spectrum of available pharmacological treatments, two different classes of medication, a2-adrenergic agonists and antipsychotics are primarily recommended.

Clinical Overview

Restless legs syndrome (RLS) is a neurological movement disorder characterized by a compelling urge to move the legs usually accompanied by an uncomfortable and unpleasant sensations.

Symptoms begin or worsen during periods of rest or inactivity, are partially or totally relieved by movement, and are worse in the evening or at night. Despite being a common disorder, RLS is generally underdiagnosed. The prevalence of RLS in the general population is 5%–10%, making it the most common movement disorder.

Prevalence increases with advancing age and the condition is observed more frequently in women. Delayed sleep onset, multiple awakenings, and a reduction in sleep efficiency all contribute to significant sleep disturbance in these patients. RLS can be idiopathic and begin at any age, or secondary to conditions such as, iron deficiency, renal failure, neuropathy, and normal pregnancy.

Although the etiology of RLS is still unclear, evidence suggests that the symptoms result from central dopaminergic dysfunction. Although results should be interpreted with caution, brain-imaging studies have shown abnormal dopamine receptor binding and dopamine hypoactivity. Iron deficiency has also been implicated in the etiology of RLS.

Dopamine agonists and l-dopa have demonstrated efficacy in the management of RLS and in contrast, certain agents that block the dopaminergic system aggravate RLS symptoms. Other known treatments for RLS include gabapentin, benzopdiazepines, and opiates.

Clinical Overview

Gait disorders are common, present in more than half of non-bedbound patients on neurology inpatient service, present in over 20% of geriatric patients (increasing with age) and are frequent reasons for a movement disorder outpatient consultation. Gait and balance are connected, complex sensorimotor behaviors that are automatic in nature but guided by cognitive (executive) and affective functions. They involve several sensory, motor and cognitive systems that allow for smooth locomotion, sustained balance, and ability to adapt to the environment. Abnormalities of gait and balance can be caused by peripheral and central nervous system disorders, from motor weakness and sensory loss, to loss of automaticity to cognitive decline. The consequences of gait dysfunction are serious: in some falling with secondary injury, and others, slow and insecure gait with a ‘fear of falling’ and need for assistive devices, all ultimately resulting in social isolation and reduced activity. Gait disorders predict poor quality of life and increased morbidity and mortality. In assessing fall risk the presence of a prior fall in the last 6 to 12 months is the best predictor. Falls are the result of many causes and the most common cause for injury related hospital admissions.

Several classification schemes have been devised for gait disorders: they can be classified according to the nervous system complexity level – lower, middle, and higher level; anatomic lesions location (i.e. cerebellar, frontal lobe etc); by cause (i.e. vascular disease, degenerative parkinsonism, spinocerebellar ataxias) and finally by its clinical phenomenology (i.e. ataxia, parkinsonism, dyskinesia). Gait disturbances may also be sub-classified as continuous (appearing whenever the patient walks) or episodic, such as festination and freezing.

Most gait disturbances can be diagnosed and classified after obtaining a good history and performing a detailed physical and neurological exam including watching the gait. For many, the diagnosis can be straightforward due to specific patterns of stepping, such as the wide base and varied step length and speed in ataxic gait, slow, small shuffling steps with decreased arm swing in parkinsonian gait and those due to spasticity, weakness and sensory loss. However, in some the cause is not clear and appears to take on features of several types of problems and anatomic origins (multifactorial gait disorders) or is bizarre in character, and the diagnosis is not clear. Some of those with bizarre features may be of a functional etiology.

Detailed assessment with ambulatory gait monitoring devices, gait mats or in a sophisticated gait laboratory are justified to make a diagnosis in some cases, prior to surgery to help document or identify impairments, to document subtle changes over time and for therapeutic effects, though they are more used as a research tool. Wearable devices are gaining increased interest to assess gait issues and falls. Cognitive and fall risk assessment are essential parts of the evaluation of a patient with gait disturbance including internal and external risk factors.

Treatment of gait disturbances depends on the underlying cause. It is important to review the patient’s medication list to be assured the problem is not drug-induced, such as drug-induced parkinsonism related to antipsychotics. Treatment should include active interventions to decrease fall risk which may include medical (for spasticity, dystonia, parkinsonism, or chorea), surgical and physical therapy interventions which usually are given simultaneously.

Clinical Overview

Spasticity is a feature of various neurologic conditions due to the loss of inhibition of motor neurons. It clinically presents with a variable combination of paralysis, increased tendon reflex activity (hyperreflexia with brisk reflexes and a positive Babinski sign) and hypertonia (as opposed to rigidity seen as a characteristic feature of parkinsonism). Clonus (most commonly present in the ankle) may be present and presents as involuntary, rhythmic, muscular contractions and relaxations.

Pathophysiologically, the stretch reflex may play a key role in the imbalance between the excitatory and inhibitory inputs to α motor neurons.

Common causes of spasticity include developmental or acquired lesions of the pyramidal tract in the brain and/or spinal cord in the context of cerebral palsy, stroke, multiple sclerosis, trauma, and others.

Spasticity is a common and significant cause of reduced quality of life and independence. Falls are one of the most important consequences (also see: gait disorders).

Evaluation and management of spasticity should focus first on excluding symptomatic causes. After correction of symptomatic causes, management is typically supportive but may include physical and occupational. Specific agents which may improve include GABA receptor agonists, e.g. baclofen or benzodiazepines, e.g. clonazepam, or ryanodine receptor anatagonists, e.g. dantrolene or botulinum toxin.

Clinical Overview

Stiff Person Syndrome (SPS) is a rare autoimmune movement disorder that affects central nervous system and is clinically characterized by muscle stiffness, spasms and increased startle response (unconscious defensive response) to unexpected stimuli.

SPS belongs to the group of Stiff person syndrome spectrum disorders (SPSD) that share the same clinical features and spectrum of antibodies against neuronal proteins, that participate in normal inhibition of central hyperexcitability which explains its clinical characteristics. The exact pathophysiological mechanism is still not known.

Muscle stiffness usually begins insidously in lower back and legs and can mimic lower back pain, but in time tends to progress to other body parts, mainly to distal limb parts and abdominal muscles. As a result patients present with typical “stiff” or “robotic” gait with exaggerated lumbar hyperlordosis. Stiffness usually resolves in sleep or under anesthesia.

Muscle spasms in SPS are painful and intermittent. They typically occur as a result of unexpected external stimuli, mainly to tactile, acoustic or emotional stimulus and usually last for few seconds or minutes. Extreme spasms can lead to spontaneous fractures and joint subluxations or uncontrolled falls of the person with typical “log-like” falling down.

Patients with SPS also often manifest non-motor features such as anxiety, depression and task specific phobias. The most common is agoraphobia, with fear of falling down if walking unaided. Also, there can be transient symptoms of autonomic dysfunction leading to sympathetic hyperactivity with diaphoresis, hyperpyrexia or sexual dysfunctions.

Besides classical SPS there are focal forms of disease when symptoms are isolated on one body part, e.g. Stiff limb syndrome, or forms associated with additional neurological features (e.g. epilepsy, ataxia, polyneuropathy) and also fulminant and sometimes fatal forms such as Progressive encephalomyelopathy with rigidity and myoclonus (PERM).

Diagnosis of SPS is based on its clinical presentation. Findings of elevated standard antibodies titres against GAD, glycine, DPPX, GABARAP, gephyrin and ampiphysine in cerebrospinal fluid and blood may be helpful but are not crucial for the diagnosis. EMG studies show unspecific continuous motor unit activity potentials (CMAP) in affected muscles. Electrophysiological studies of exteroceptive reflexes with abnormal masseter inhibitory reflex with loss of S2 component, and shortened latency of R2 recovery in Blink reflex are more specific.

Brain and spine MRI are normal and are used only to exclude other possible diagnoses.

SPS is commonly associated with other autoimmune diseases, including vitiligo, diabetes mellitus and thyroiditis. Some forms (mainly associated with anti-ampiphysin antibodies) may be associated with neoplasms.

The therapy of SPSD is based on the triad of symptomatic treatment, immunotherapy, and tumor removal/oncological treatment where appropriate.

Symptomatic treatment is based on drugs with GABA-ergic action. Nevertheless, due to its autoimmune nature, the core treatment is immunotherapy utilizing corticosteroids, intravenous immunoglobulins (IVIG) and/or plasma exchange as first line therapy, escalated to second line immunotherapy utilizing e.g. cyklosporin, cyklofosfamid or mycofenolat mofetil in unresponsive cases. Treatment of the underlying oncological process is crucial in cases with paraneoplastic association.

The prognosis of the disease is variable.