Boala Alzheimer

Boala Alzheimer (Morbus Alzheimer) este o afeciune degenerativ progresiv a creierului care apare mai ales la persoane de vrst naintat, producnd o deteriorare din ce n ce mai accentuat a funciilor de cunoatere ale creierului, cu pierderea capacit ilor intelectuale ale individului i a valorii sociale a personalitii sale, asociat cu tulburri de comportament, ceea ce realizeaz starea cunoscut sub numele de demen (din latin: demens). Boala i modificrile organice din creier care o nsoesc au fost descrise pentru prima dat de Alois Alzheimer, psihiatru i neuropatolog german. Denumirea de boal Alzheimer a fost utilizat pentru prima dat de psihiatrul german Emil Kraepelin n manualul su de psihiatrie ("Lehrbuch der Psychiatrie", 1911). Aceast boal reprezint forma cea mai comun de declin mintal la persoanele n vrst i a devenit tot mai frecvent o dat cu creterea longevitii. La 25 noiembrie 1901, psihiatrul german Alois Alzheimer examineaz pentru prima dat o pacient, Auguste D., n vrst de 51 de ani, internat n "Spitalul pentru Bolnavi psihici i Epileptici" din Frankfurt pentru tulburri cognitive progresive, halucinaii, idei delirante i degradare a personalitii sociale. Alzheimer noteaz la nceput un diagnostic vag: "Boal a uitrii" (Krankheit des Vergessens). Evoluia bolii este urmrit timp de cinci ani i, dup moartea pacientei n urma unei infecii, creierul obinut n urma autopsiei este examinat cu amnunime de Alzheimer, descoperind modificri caracteristice necunoscute pn atunci. Cazul este prezentat pe 3 noiembrie 1906 la a 37a Conferin a Psihiatrilor Germani din Sud-Vest inut la Tbingen i publicat n revista de specialitate "Allgemeine Zeitschrift fr Psychiatrie und Psychisch-Gerichtliche Medizin" (1907, vol. 64, pp. 146-48) sub titlul Eine eigenartige Erkrankung der Hirnrinde ("O mbolnvire particular a scoarei creierului").

Inciden i debut
Boala Alzheimer este cea mai frecvent form de demen la persoanele n vrst i reprezint jumtate din totalitatea cazurilor de demen. Pentru rile europene se estimeaz c la persoanele n vrst de 65 de ani frecvena bolii Alzheimer este de ca. 23%, la vrsta de 70 de ani 3%, la 75 de ani 6%, iar peste 85 de ani 25-40%. ntr-un studiu recent denumit "PAQUID" efectuat n Frana, s-a constatat c 17,8% din persoanele trecute de 75 de ani sunt atinse de boala Alzheimer sau de o form nrudit de demen. Potrivit statisticilor din Romnia, incidena tulburrilor mintale a crescut de la 605,2 persoane la 100.000 de locuitori n 1975, la 883,3 persoane / 100.000 de locuitori n 1993, fr a avea date asupra cazurilor de demen. n cazul unui debut precoce, nainte de vrsta de 65 de ani - ca n cazul princeps al lui Alzheimer - se folosete termenul de "demen presenil", cazurile aprute tardiv, la persoane n vrst de peste 70 de ani, corespund noiunii mai vechi de "demen senil".

Manifestri clinice
Manifestarea cea mai caracteristic a bolii este demena cu caracter progresiv. Pierderea memoriei este de cele mai multe ori primul semn ngrijortor al bolii Alzheimer

Simptome cognitive

Tulburri de memorie: dificultatea de a-i reaminti informaii anterior nvate i imposibilitatea de a acumula informaii noi. Primele care se pierd sunt evenimentele recente, n timp ce amintirile vechi pot fi conservate. Tulburri de vorbire: bolnavul nu i mai gsete cuvintele, chiar pentru noiuni simple. Incapacitatea de a efectua diferite activiti motorii coordonate: bolnavul "nu mai tie" cum s se mbrace adecvat, cum se descuie ua cu cheia etc. Imposibilitatea de a recunoate, identifica i denumi obiecte uzuale. Tulburri ale funciilor de organizare a activitilor zilnice, incapacitatea de a lua decizii. Probleme legate de gndirea abstract, tulburri de calcul, dezorientare temporal i spaial, pierderea iniiativelor. False recunoateri: la nceput dificultate n recunoaterea fizionimiilor cunoscute, urmat de identificri eronate, care pot provoca stri de anxietate.

Aceste simptome se caracterizeaz printr-un debut gradat, bolnavul dezvolt anumite strategii pentru a-i disimula dificultile, pentru un anumit timp i pstreaz o "faad" neltoare, declinul ns se agraveaz progresiv.

Simptome non-cognitive

Agitaie i agresivitate fizic sau verbal. Tulburri psihotice: halucinaii, de obicei vizuale, idei delirante (de persecuie, de gelozie, de abandon etc.). Tulburri ale dispoziiei afective: n principal depresie i anxietate, mai rar stri de euforie exagerat. Tulburri ale comportamentului alimentar: reducere sau cretere exagerat a apetitului, alimentaie nengrijit, ingerare de substane non-alimentare. Dezinhibiie sexual: comentarii pe teme sexuale, gesturi obscene, mai rar agresivitate sexual. Incontinen urinar i pentru materii fecale, satisfacerea nevoilor fiziologice n locuri neadecvate sau n prezena altor persoane

Nu se cunoate cu siguran cauza care provoac boala Alzheimer, dar este posibil s existe mai multe cauze care concur la apariia bolii.

Factori de risc - Vrsta naintat este factorul de risc cel mai important, dar nu exist nicio dovad c boala Alzheimer ar fi cauzat de procesul biologic de mbtrnire. - Factori nocivi pentru aparatul cardio-vascular: diabetul, hipertensiunea arterial, nivel crescut de colesterol, fumatul (presupunerea c nicotina ar fi protectiv mpotriva bolii Alzheimer s-a dovedit nefondat)[Nicotina este una din cauzele aparitiei bolii]. - Nivel crescut de homocistein n snge, asociat cu un nivel sczut de vitamin B12 i acid folic. - Expunerea la metale uoare (de ex. deodorani cu aluminiu), presupunere care nu este unanim acceptat. Aluminiul, cu efecte neurotoxice, se gsete adesea n cantiti mari n creierele bolnavilor decedai cu demen Alzheimer, dar nu se poate dovedi o relaie cauzal. - Traumatisme cranio-cerebrale repetate grave. - Unele bacterii (Chlamidii) i unele virusuri (slow-virus) ar favoriza formarea de plci senile. Factori genetici - Exist cazuri ereditare rare cauzate de prezena unei gene dominante n unele familii. Se apreciaz c persoanele avnd o rud de gradul I care sufer de boala Alzheimer se afl n risc teoretic absolut de 26% pn la 45%. Mutaii ale presenilinei 1 (PS1) pe cromozomul 14 i ale presenilinei 2 (PS2) pe cromozomul 1 duc la o form foarte agresiv n cazurile familiale de boal. Presenilinele au fost identificate ca pri componente eseniale n procesul proteolitic prin care se produce beta-amiloid prin fragmentarea de APP (Amiloid Precursor Protein), legat de cromozomul 21. - Boala Alzheimer este n legtur cu cromozomii 1, 14 i 21 (trisomia 21 reprezint cauza sindromului Down), dar este posibil s existe i alte legturi cromozomiale. Genotipul ApoE ipsilon 4, legat de cromozomul 19, protein care particip la transportul colesterolului i intervine n procesele de reparaie neuronal, este considerat factor predispozant pentru cazurile sporadice de boal Alzheimer. - Thomas Arendt i colab. de la Institutul "Paul-Flechsig fr Hirnforschung" din Leipzig au constatat recent (2010) c deja n copilrie ar exista modificri n creier, care ar indica probabilitatea apariiei mai trziu a bolii Alzheimer. Creierul acestor persoane conine un numr crescut de celule hiperploide (celule cu mai multe perechi de cromozomi n diverse combinaii), care ar contribui la moartea celular n creierul bolnavilor cu morbul Alzheimer.

Alzheimer's disease
"Alzheimer" redirects here. For other uses, see Alzheimer (disambiguation). Alzheimer's disease (AD), also known in medical literature as Alzheimer disease, is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death. It was first described by German psychiatrist and neuropathologist Alois Alzheimer in 1906 and was named after him. Most often, AD is diagnosed in people over 65 years of age, although the less-prevalent early-onset Alzheimer's can occur much earlier. In 2006, there were 26.6 million sufferers worldwide. Alzheimer's is predicted to affect 1 in 85 people globally by 2050. Although Alzheimer's disease develops differently for every individual, there are many common symptoms. Early symptoms are often mistakenly thought to be 'agerelated' concerns, or manifestations of stress. In the early stages, the most common symptom is difficulty in remembering recent events. When AD is suspected, the diagnosis is usually confirmed with tests that evaluate behaviour and thinking abilities, often followed by a brain scan if available. As the disease advances, symptoms can include confusion, irritability and aggression, mood swings, trouble with language, and long-term memory loss. As the sufferer declines they often withdraw from family and society. Gradually, bodily functions are lost, ultimately leading to death. Since the disease is different for each individual, predicting how it will affect the person is difficult. AD develops for an unknown and variable amount of time before becoming fully apparent, and it can progress undiagnosed for years. On average, the life expectancy following diagnosis is approximately seven years. Fewer than three percent of individuals live more than fourteen years after diagnosis. The cause and progression of Alzheimer's disease are not well understood. Research indicates that the disease is associated with plaques and tangles in the brain. Current treatments only help with the symptoms of the disease. There are no available treatments that stop or reverse the progression of the disease. As of 2012, more than 1000 clinical trials have been or are being conducted to find ways to treat the disease, but it is unknown if any of the tested treatments will work. Mental stimulation, exercise, and a balanced diet have been suggested as ways to delay cognitive symptoms (though not brain pathology) in healthy older individuals, but there is no conclusive evidence supporting an effect. Because AD cannot be cured and is degenerative, the sufferer relies on others for assistance. The role of the main caregiver is often taken by the spouse or a close relative. Alzheimer's disease is known for placing a great burden on caregivers; the pressures can be wide-ranging, involving social, psychological, physical, and economic elements of the caregiver's life. In developed countries, AD is one of the most costly diseases to society.

Characteristics
The disease course is divided into four stages, with progressive patterns of cognitive and functional impairments.

Pre-dementia
The first symptoms are often mistakenly attributed to ageing or stress. Detailed neuropsychological testing can reveal mild cognitive difficulties up to eight years before a person fulfils the clinical criteria for diagnosis of AD. These early symptoms can affect the most complex daily living activities. The most noticeable deficit is memory loss, which shows up as difficulty in remembering recently learned facts and inability to acquire new information. Subtle problems with the executive functions of attentiveness, planning, flexibility, and abstract thinking, or impairments in semantic memory (memory of meanings, and concept relationships) can also be symptomatic of the early stages of AD. Apathy can be observed at this stage, and remains the most persistent neuropsychiatric symptom throughout the course of the disease. The preclinical stage of the disease has also been termed mild cognitive impairment, but whether this term corresponds to a different diagnostic stage or identifies the first step of AD is a matter of dispute.

Cause
Microscopic image of a neurofibrillary tangle, conformed by hyperphosphorylated tau protein The cause for most Alzheimer's cases is still essentially unknown (except for 1% to 5% of cases where genetic differences have been identified). Several competing hypotheses exist trying to explain the cause of the disease:

Management
There is no cure for Alzheimer's disease; available treatments offer relatively small symptomatic benefit but remain palliative in nature. Current treatments can be divided into pharmaceutical, psychosocial and caregiving.

Boala Parkinson
Salt la: Navigare, cutare Boala Parkinson este o boal degenerativ ce survine n urma distrugerii lente i progresive a neuronilor. ntruct zona afectat joac un rol important n controlul micrilor, pacienii prezint gesturi rigide, sacadate i incontrolabile, tremor i instabilitate postural. Tulburrile legate de boala Parkinson apar cel mai adesea ntre 50 i 70 ani; vrsta medie de apariie a bolii este de 57 ani. La nceput, simptomele pot fi confundate cu procesul normal de mbtrnire, dar pe msura agravrii acestora, diagnosticul devine evident. n momentul manifestrii primelor simptome, se crede c ntre 60% i 80% din celulele din zona de control a activitilor motorii sunt deja distruse. Boala Parkinson are o evoluie progresiv, iar semnele i simptomele se acumuleaz n timp. Dei aceast afeciune este potenial invalidant, ea evolueaz lent astfel nct majoritatea pacienilor beneficiaz de numeroi ani de via activ dup stabilirea diagnosticului. Mai mult, spre deosebire de alte afeciuni neurologice grave, boala Parkinson este tratabil. Tratamentul este medicamentos i chirugical dar poate consta i n implantarea unui dispozitiv pentru stimularea creierului. La scar mondial, boala este diagnosticat la 300 000 persoane n fiecare an. Incidena i prevalena bolii cresc odat cu vrsta. Boala Parkinson afecteaz 1% din persoanele cu vrsta peste 65 ani. Rareori, boala survine n copilrie sau adolescen. Incidena bolii este de 1,5 ori mai mare la brbai dect la femei. Semne i simptome Cele trei semne cardinale ale bolii Parkinson sunt: tremorul de repaus, rigiditatea i bradikinezia. Dintre acestea, dou sunt eseniale pentru stabilirea diagnosticului. Instabilitatea postural este al patrulea semn cardinal, dar survine tardiv, de obicei dup 8 ani de evoluie a bolii. n 70% din cazuri, gesturile ritmice incontrolabile ale minilor, capului sau picioarelor constituie primul simptom i se manifest n special n repaus i n perioadele de stres. Tremorul este diminuat n timpul micrilor i dispare n somn, este accentuat de stres i de oboseal. Tremorul devine mai puin evident pe masura evoluiei bolii. Rigiditatea se refer la creterea rezistenei la mobilizarea pasiv a muchilor i este mai evident la micrile voluntare ale membrului contralateral. Bradikinezia se refer la lentoarea micrilor, dar include i scderea micrilor spontane i scderea amplitudinii micrilor. Bradikinezia este vizibil prin micrografie (scris de mn mic, ilizibil), hipomimie (diminuarea micrilor mimice), clipit rar i hipofonie (voce diminuat).

Instabilitatea postural se refer la tulburrile de echilibru i coordonare. Apariia sa este o etapa important n evoluia bolii, deoarece instabilitatea postural este dificil tratabila i este o sursa comun de invaliditate n stadiile avansate ale bolii. Demena survine tardiv n evoluia bolii Parkinson i afecteaz 15% - 30% din pacieni. Memoria recent este afectat.

Alte semne sunt:

tulburri ale somnului dificulti la deglutiie sialoree (salivaie abundent) micrografie (scris mic, ilizibil) hipofonie (voce diminuat, monoton) i dificulti la articularea cuvintelor incontinen urinar i constipaie, datorit alterarii funciei intestinului i vezicii confuzie, pierderea memoriei tulburri ale mersului, cu pai mici, trii; tendina accentuat spre cdere prin pierderea reflexelor posturale pierderea balansului braelor n timpul mersului hipotensiune ortostatic dermatit seboreic modificri ale personalitii

Cauze i factori de risc

Celulele nervoase afectate de boala Parkinson sunt situate ntr-o zon numit substantia nigra (substana neagr) din centrul creierului. Aceste celule produc dopamin, un neurotransmitor care permite controlarea micrilor. Prin moartea celulelor din substana neagr, boala Parkinson creeaz un deficit de dopamin. n mod normal, controlul micrilor este rezultatul unui echilibru dintre cantitatea de dopamin i acetilcolin (un alt neurotransmitor). Prin pierderea acestui echilibru, rezult tremorul, rigiditatea i pierderea coordonrii. Cauza pierderii progresive a neuronilor n boala Parkinson rmne ns necunoscut. Oamenii de tiin indic o asociere dintre factorii de mediu i cei genetici. Factorii de mediu: expunerea precoce sau prelungit la substane poluante chimice sau la pesticide (ierbicide i insecticide) consumul unui drog (MPTP) poate cauza semnele i simptomele bolii Parkinson drogul are un efect similar pesticidelor medicamente neuroleptice (fenotiazina) sau substanele care blocheaz receptorii de dopamin intoxicaia cu monoxid de carbon sau cu mangan

hidrocefalia, tumorile craniene, hematom subdural, boala Wilson, tulburrile idiopatice degenerative Factorii genetici: toate cauzele genetice cunoscute explica mai puin de 5% din cazurile de Parkinson

Kinetoterapia i ortofonia
Kinetoterapia este un adjuvant terapeutic important i const n exerciii fizice zilnice i gimnastic, reeducare funcional, refacerea echilibrului postural etc. Ortofonia permite tratarea disartriei (tulburri de vorbire), datorate unei articulaii dificile.

Parkinson's disease

Parkinson's" redirects here. For other uses, see Parkinson's (disambiguation). Parkinson's disease (also known as Parkinson disease, Parkinson's, idiopathic parkinsonism, primary parkinsonism, PD, hypokinetic rigid syndrome/HRS, or paralysis agitans) is a degenerative disorder of the central nervous system. The motor symptoms of Parkinson's disease result from the death of dopamine-generating cells in the substantia nigra, a region of the midbrain; the cause of this cell death is unknown. Early in the course of the disease, the most obvious symptoms are movement-related; these include shaking, rigidity, slowness of movement and difficulty with walking and gait. Later, cognitive and behavioural problems may arise, with dementia commonly occurring in the advanced stages of the disease. Other symptoms include sensory, sleep and emotional problems. PD is more common in the elderly, with most cases occurring after the age of 50. The main motor symptoms are collectively called parkinsonism, or a "parkinsonian syndrome". Parkinson's disease is often defined as a parkinsonian syndrome that is idiopathic (having no known cause), although some atypical cases have a genetic origin. Many risk and protective factors have been investigated: the clearest evidence is for an increased risk of PD in people exposed to certain pesticides and a reduced risk in tobacco smokers. The pathology of the disease is characterized by the accumulation of a protein

called alpha-synuclein into inclusions called Lewy bodies in neurons, and from insufficient formation and activity of dopamine produced in certain neurons within parts of the midbrain. Lewy bodies are the pathological hallmark of the idiopathic disorder, and the distribution of the Lewy bodies throughout the Parkinsonian brain varies from one individual to another. The anatomical distribution of the Lewy bodies is often directly related to the expression and degree of the clinical symptoms of each individual. Diagnosis of typical cases is mainly based on symptoms, with tests such as neuroimaging being used for confirmation. Modern treatments are effective at managing the early motor symptoms of the disease, mainly through the use of levodopa and dopamine agonists. As the disease progresses and dopaminergic neurons continue to be lost, these drugs eventually become ineffective at treating the symptoms and at the same time produce a complication called dyskinesia, marked by involuntary writhing movements. Diet and some forms of rehabilitation have shown some effectiveness at alleviating symptoms. Surgery and deep brain stimulation have been used to reduce motor symptoms as a last resort in severe cases where drugs are ineffective. Research directions include investigations into new animal models of the disease and of the potential usefulness of gene therapy, stem cell transplants and neuroprotective agents. Medications to treat non-movement-related symptoms of PD, such as sleep disturbances and emotional problems, also exist. The disease is named after the English doctor James Parkinson, who published the first detailed description in An Essay on the Shaking Palsy in 1817. Several major organizations promote research and improvement of quality of life of those with the disease and their families. Public awareness campaigns include Parkinson's disease day (on the birthday of James Parkinson, April 11) and the use of a red tulip as the symbol of the disease. People with parkinsonism who have enhanced the public's awareness include Michael J. Fox and Muhammad Ali.

Classification
The term parkinsonism is used for a motor syndrome whose main symptoms are tremor at rest, stiffness, slowing of movement and postural instability. Parkinsonian syndromes can be divided into four subtypes according to their origin: primary or idiopathic, secondary or acquired, hereditary parkinsonism, and parkinson plus syndromes or multiple system degeneration.[1] Parkinson's disease is the most common form of parkinsonism and is usually defined as "primary" parkinsonism, meaning parkinsonism with no external identifiable cause.[2][3] In recent years several genes that are directly related to some cases of Parkinson's disease have been discovered. As much as this conflicts with the definition of Parkinson's disease as an idiopathic illness, genetic parkinsonism disorders with a similar clinical course to PD are generally included under the Parkinson's disease label. The terms "familial Parkinson's disease" and "sporadic Parkinson's disease" can be used to differentiate genetic from truly idiopathic forms of the disease.[4] Usually classified as a movement disorder, PD also gives rise to several non-motor types of symptoms such as sensory deficits,[5] cognitive difficulties or sleep problems.

Parkinson plus diseases are primary parkinsonisms which present additional features.[2] They include multiple system atrophy, progressive supranuclear palsy, corticobasal degeneration and dementia with Lewy bodies.[2][6] In terms of pathophysiology, PD is considered a synucleinopathy due to an abnormal accumulation of alpha-synuclein protein in the brain in the form of Lewy bodies, as opposed to other diseases such as Alzheimer's disease where the brain accumulates tau protein in the form of neurofibrillary tangles.[7] Nevertheless, there is clinical and pathological overlap between tauopathies and synucleinopathies. The most typical symptom of Alzheimer's disease, dementia, occurs in advanced stages of PD, while it is common to find neurofibrillary tangles in brains affected by PD.[7] Dementia with Lewy bodies (DLB) is another synucleinopathy that has similarities with PD, and especially with the subset of PD cases with dementia. However the relationship between PD and DLB is complex and still has to be clarified.[8] They may represent parts of a continuum or they may be separate diseases.

Signs and symptoms

Main article: Signs and symptoms of Parkinson's disease Parkinson's disease affects movement, producing motor symptoms.[1] Non-motor symptoms, which include autonomic dysfunction, neuropsychiatric problems (mood, cognition, behavior or thought alterations), and sensory and sleep difficulties, are also common.[1]

Motor
A man with Parkinson's disease displaying a flexed walking posture pictured in 1892. Photo appeared in Nouvelle Iconographie de la Salptrire, vol. 5.

Handwriting of a person affected by PD in Lectures on the diseases of the nervous system by Charcot (1879). The original description of the text states "The strokes forming the letters are very irregular and sinuous, whilst the irregularities and sinuosities are of a very limited width. (...) the down-strokes are all, with the exception of the first letter, made with comparative firmness and are, in fact, nearly normal the finer up-strokes, on the contrary, are all tremulous in appearance (...)." Further information: Parkinsonian gait Four motor symptoms are considered cardinal in PD: tremor, rigidity, slowness of movement, and postural instability.[1]

Tremor is the most apparent and well-known symptom.[1] It is the most common; though around 30% of individuals with PD do not have tremor at disease onset, most develop it as the disease progresses.[1] It is usually a rest tremor: maximal when the limb is at rest and disappearing with voluntary movement and sleep.[1] It affects to a greater extent the most distal part of the limb and at onset typically appears in only a single arm or leg, becoming bilateral later.[1] Frequency of PD tremor is between 4 and 6 hertz (cycles per second). A feature of tremor is pill-rolling, the tendency of the index finger of the hand to get into contact with the thumb and perform together a circular movement.[1][9] The term derives from the similarity between the movement in PD patients and the earlier pharmaceutical technique of manually making pills.[9] Bradykinesia (slowness of movement) is another characteristic feature of PD, and is associated with difficulties along the whole course of the movement process, from planning to initiation and finally execution of a movement.[1] Performance of sequential and simultaneous movement is hindered.[1] Bradykinesia is the most disabling symptom in the early stages of the disease.[2] Initial manifestations are problems when performing daily tasks which require fine motor control such as writing, sewing or getting dressed.[1] Clinical evaluation is based in similar tasks such as alternating movements between both hands or both feet.[2] Bradykinesia is not equal for all movements or times. It is modified by the activity or emotional state of the subject, to the point that some patients are barely able to walk yet can still ride a bicycle.[1] Generally patients have less difficulty when some sort of external cue is provided.[1][10] Rigidity is stiffness and resistance to limb movement caused by increased muscle tone, an excessive and continuous contraction of muscles.[1] In parkinsonism the rigidity can be uniform (lead-pipe rigidity) or ratchety (cogwheel rigidity).[1][2][11][12] The combination of tremor and increased tone is considered to be at the origin of cogwheel rigidity.[13] Rigidity may be associated with joint pain; such pain being a frequent initial manifestation of the disease.[1] In early stages of Parkinson's disease, rigidity is often asymmetrical and it tends to affect the neck and shoulder muscles prior to the muscles of the face and extremities.[14] With the progression of the disease, rigidity typically affects the whole body and reduces the ability to move. Postural instability is typical in the late stages of the disease, leading to impaired balance and frequent falls, and secondarily to bone fractures.[1] Instability is often absent in the initial stages, especially in younger people.[2] Up to 40% of the patients may experience falls and around 10% may have falls weekly, with number of falls being related to the severity of PD.[1] Other recognized motor signs and symptoms include gait and posture disturbances such as festination (rapid shuffling steps and a forward-flexed posture when walking),[1] speech and swallowing disturbances including voice disorders,[15] mask-like face expression or small handwriting, although the range of possible motor problems that can appear is large.[1

Management

Main article: Management of Parkinson's disease There is no cure for Parkinson's disease, but medications, surgery and multidisciplinary management can provide relief from the symptoms. The main families of drugs useful for treating motor symptoms are levodopa (usually combined with a dopa decarboxylase inhibitor or COMT inhibitor), dopamine agonists and MAO-B inhibitors.[33] The stage of the disease determines which group is most useful. Two stages are usually distinguished: an initial stage in which the individual with PD has already developed some disability for which he needs pharmacological treatment, then a second stage in which an individual develops motor complications related to levodopa usage.[33] Treatment in the initial stage aims for an optimal tradeoff between good symptom control and side-effects resulting from enhancement of dopaminergic function. The start of levodopa (or L-DOPA) treatment may be delayed by using other medications such as MAO-B inhibitors and dopamine agonists, in the hope of delaying the onset of dyskinesias.[33] In the second stage the aim is to reduce symptoms while controlling fluctuations of the response to medication. Sudden withdrawals from medication or overuse have to be managed.[33] When medications are not enough to control symptoms, surgery and deep brain stimulation can be of use.[34] In the final stages of the disease, palliative care is provided to enhance quality of life.

Risk factors
U.S. Army helicopter spraying Agent Orange over Vietnamese agricultural land during the Vietnam war. Agent Orange has been associated with PD. Injections of the synthetic neurotoxin MPTP produce a range of symptoms similar to those of PD as well as selective damage to the dopaminergic neurons in the substantia nigra. This observation has led to theorizing that exposure to some environmental toxins may increase the risk of having PD.[62] Exposure to toxins that have been consistently related to the disease can double the risk of PD, and include certain pesticides, such as rotenone or paraquat, and herbicides, such as Agent Orange.[62][63][64] Indirect measures of exposure, such as living in rural environments, have been found to increase the risk of PD.[64] Heavy metals exposure has been proposed to be a risk factor, through possible accumulation in the substantia nigra; however, studies on the issue have been inconclusive.