Parkinson’ s Disease & Other Movement Disorders’ Center

The Center for Parkinson’s Disease and other Movement Disorders of Mediterraneo was established in order to offer comprehensive health care to patients with Parkinson’s disease as well as other movement and accompanying problems. His main goal is the cooperation of the specialists of the interdisciplinary medical team for a targeted and personalized therapeutic treatment of each patient. The interdisciplinary medical team includes specialties such as:

• Neurology and Neurophysiology of Movement Disorders
• Stereotactic Neurosurgery
• Stereotactic Radiosurgery
• Neuroradiology
• Nuclear Medicine
• Microbiology/ Biology
• Invasive Gastroenterology
• Neuropshycology
• Physical Medical Rehabilitation
• Dietetics
• Collaboration with other medical specialties for coexisting diseases and non-motor symptoms such as urological problems, orthostatic hypotension, musculoskeletal problems, etc.

1. Parkinson’s disease, and other extrapyramidal or parkinsonian syndromes. Multiple System Atrophy, Progressive Supranuclear Palsy, Corticobasal Degeneration, Lewy Body Dementia.
2. Movement disorders of various etiologies such as various tremors, dystonias (headache, writer’s cramp, hereditary dystonias, etc.), chorea, myoclonus, athetosis, ballismus, paroxysmal movement disorders, akathisia, tics, etc.

3. Dementias and other neyropsychiatric syndromes with movement disorders such as Chorea (Huntington), Wilson’s disease, Frontotemporal dementia, and other hereditary and degenerative diseases (diseases with iron metabolism disorder, neuroacanthocytosis, tremor/ataxia related to fragile X, etc.).

4. Movement disorders secondary to cerebral palsy, stroke, dementia and multiple sclerosis.

Some of the most common movement disorders are listed below:

Parkinson’s disease is the most common extrapyramidal disorder and the most common degenerative disease after Alzheimer’s. It develops chronically with a clinical picture which consists of motor (bradykinesia, tremors, stiffness, instability) and non-motor symptoms (depression, sleep disorders, orthostatic hypotension, mental disorders, etc.) and which, together with the adverse effects of medication, lead to deep time in the need for continuous treatment of this. 35%-42% of cases remain undiagnosed! In Greece we estimate 25,000-30,000 parkinsonians. A significant percentage of these will need to undergo invasive or device-assisted treatments.

Huntington’s disease (HD): HD is a genetic (inherited) disease. Men and women are equally likely to inherit the gene and develop the disease. In 1993, we identified the gene that causes HD and we can now detect it. In most cases, the symptoms of the disease appear in middle adulthood. The main symptoms are involuntary dance-like movements and tremors (chorea), mental disorders and mental disorders. Today, its treatment has progressed significantly.

Tremor is the most common movement disorder. Its classification is clinical and based on phenomenological characteristics such as location, its relative prevalence when the limb is at rest (tremor at rest or quiescence), when gravity acts on the limb (position tremor), as well as when the limb manifests motor activity (fear of action or purpose). Other characteristics of it are its range, frequency but also its coexistence with additional symptoms which may refer to parkinsonism, neuropathy, metabolic or genetic disorder, etc. A variety of tremor is the so-called Idiopathic Tremor, which is generally considered to be a late progressive inherited disorder. Over time, tremors can become more intense and spread from the hands to other areas of the body such as the head. It often interferes with daily activities (eating, personal hygiene, various skills) and creates problems.

Dystonia is a disorder of muscle tone characterized by “Persistent muscle contractions of a specific movement pattern and direction, which cause abnormal, often rotational positions or repetitive movements” These repetitive movements often take on the character of a tremor (shaking) and then we’re talking about dystonic tremor. Recently onset dystonia always needs investigation in order to find its cause.

The most common dystonias are those localized in some part of the body, such as cervical (neck) dystonia, spasm of the eyelids (blepharospasm), face and mouth (craniofacial, orofacial dystonia-Meige syndrome), hand dystonia in the case of writer’s or musician’s cramp (violinist, guitarist, pianist etc).

The diagnosis of movement disorders such as Parkinson’s disease is made by clinical examination but also by ancillary/laboratory methods according to the criteria of international scientific societies  and organizations such as the UK Brain Bank Criteria, and the International Movement Disorders Society Criteria.

But what plays an important role from the first appointment is the good medical history and the narration/opinion of the patient and his family, about the burden of the disease. The role of the practitioner is to listen carefully in order to be able to individualize and adapt the entire treatment accordingly to the patient’s measures.

Ancillary/laboratory testing includes:

1. Brain scintigraphic tests [123I]FP-CIT (Ioflupane) and (IBZM) SPECT as well as myocardial scintigraphy with meta-iodobenzylguanidine (123I-MIBG). The F-dopa PET (positron emission tomography) test is also important in this direction.
2. Conventional as well as the latest MRI volumetric techniques (techniques for assessing cerebral atrophy), as well as other quantitative structural techniques (DWI & MTI, DTT) etc. have significantly contributed to the diagnosis and differential diagnosis.
3. Transcranial ultrasound is an important method for assessing even the initial stages of Parkinson’s disease, which can assess the echogenicity of midbrain structures such as the substantia nigra, the area mainly damaged in Parkinson’s.
4. Sleep study with a multi-recording method to highlight sleep disorders which are useful indicators for the treatment of Parkinson’s disease. Such a very important disorder, which should always be treated, occurs during the REM stage of sleep and is called Rem Behavior Disorder.
5. Wearable devices for recording the motor parameters of patients in their daily life and activity, as objective indicators for monitoring their motor condition (motor skills, walking, mobility disorders, instability, etc.)
6. Efficacy test of specific antiparkinsonian drugs.
7. Smell disorder such as this can be demonstrated with tests such as the University of Pennsylvania Smell Identification Test (UPSIT) and “Sniffin’ Sticks” seem to be quite a useful method.
8. Genetic Testing of monogenic diseases, microarrays, Next Generation Sequencing-NGS for specific mutations (with technology for marking the responsible regions of the genome and neighboring exons), as well as Whole Exome Sequencing-WES (genome analysis). Also recently, the search for valid Biomarkers in blood and Cerebrospinal fluid with modern methods such as the highly sensitive and specific SIMOA (single molecule array) and RT-QuIC (real-time quaking-induced conversion) techniques, has a lot to offer in the field the diagnosis and monitoring of neurological diseases.
9. Screening of anti-neuronal antibodies for the immunological and paraneoplastic etiology of movement disorders.
10. In recent years, at the level of diagnosis as well as follow-up, intense efforts are being made to develop other biomarkers for Parkinson’s disease such as saliva biopsy, OCT (ocular coherence tomography) etc.

Every therapeutic approach to the patient should include its etiological and symptomatic treatment.

A.Non-invasive methods:

Pharmaceutical treatment

• Neuroprotection (modification/slowing down of disease progression)
• Improvement of Symptoms (improvement of quality of life)
• Use of special objective assessment scales/tests

Non-pharmacological treatment

• Continuous information (patient and family) about the disease and its problems
• Support (family-society)
• Physical Education (special physical education and exercise for these diseases)

B. Invasive and/or (device-assisted) methods

• The Stereotactic Radiosurgery method which applies the technique of surface guided radiation therapy (Surface Guided Radiation Therapy, SGRT). With the help of this method we can target with great precision parts of nuclei/nodes of the brain, whose dysfunction is responsible for movement disorders such as tremor, Parkinson’s and dystonia, making selective lesions (ablations) with radiation, resulting in deactivating them without opening the skull.
• Deep Brain Stimulation-DBS and other neurosurgical operations (pallidotomy, thalamotomy).The most widely used interventions for Parkinson’s disease today are A. Inducing with heat, selective lesions in responsible dysfunctional brain nuclei/nodes and B. The superior of the lesions, Deep Brain Stimulation (DBS). The Functional and Stereotactic Neurosurgery team at the Mediterraneo hospital has a high level of expertise and a long experience in this method and constantly monitors international developments. DBS (for more information see article on interventional therapies) is now used with considerable success in other movement disorders such as dystonia (craniofacial, orofacial dystonia, segmental, generalized hereditary dystonia), essential tremor, as well as in cases of severe tics (Gilles de la Tourette syndrome), tremors after a vascular episode, etc. With DBS we achieve the pacing of dysfunctional cerebral nuclei/nodes with frequencies that promote normal movement.
• Levodopa/Carvidopa Intestinal Gel continuous infusion-LCIG after gastrostomy. For several years now, it has been possible to administer, to chronic Parkinsonian patients with motor fluctuations and hyperkinesias, levodopa in liquid form, with continuous infusion from the small intestine, with the help of a small precision pump. This mode of administration results in the creation of more stable levels of levodopa in the blood of parkinsonian patients compared to oral administration resulting in constant alleviation of parkinsonian symptoms.
• Subcutaneous pump administration of apomorphine (dopaminergic agonist) is an important method of dealing with the symptoms of the disease during the fluctuating stages of the disease. Apomorphine is an antiparkinsonian drug and should not be confused with morphine. The drug is injected subcutaneously with a needle and supported by a continuous infusion pump. It is the least invasive method and the first to be tried to a fluctuating patient. Even earlier, subcutaneous apomorphine pens (pens) can be tried during periods of time when the patient feels severely stiff and slow due to a temporary lack of effect of the oral medication (“off” state).
• The administration of botox toxin (Botox®, Disport®) mainly helps in the treatment of dystonias as mentioned above, but also other conditions such as spasticity of a limb after a Vascular Stroke, Multiple Sclerosis, Cerebral Palsy, etc. We also use it to control salivation by injection into the salivary glands, but also for digestive problems that often occur in Parkinson’s disease. A successful infusion requires quite specialized knowledge. We often use ultrasound and electromyographic guidance.

C. It should also be mentioned that therapeutic tools include:

Transcranial magnetic stimulation (TMS) and transcranial electrical (TES, tDCS) stimulation are used successfully to improve brain plasticity and are useful in treating localized dystonias such as musicians’ cramp along with dystonic limb management techniques.

Newer, invasive or non-invasive methods in various research phases, treatments targeting specific pathogenic mechanisms, genetic therapies (viral vectors carrying therapies), etc. The Clinical Research Center of the Mediterraneo Neurological Clinic often participates in clinical trials concerning the above treatments.