Intractable and rare diseases

    Last updated date: 07-May-2023

    Originally Written in English

    Intractable and Rare Diseases

    Intractable & Rare Diseases


    Neurology treats a wide variety of disorders that involve problems in the brain, spinal cord, peripheral nerves, and muscles. Neurologists diagnose and treat a wide range of diseases, from those that affect the elderly, such as Alzheimer's disease, Parkinson's disease, and stroke, to those that affect younger people, such as headache, epilepsy, encephalitis and meningitis, multiple sclerosis, myasthenia gravis, and peripheral neuropathy.

    Intractable neurological disorders, in particular, are among the most difficult to detect and treat. Intractable neurological disorders are those with an unknown cause and no proven therapeutic strategy. Motor neuron diseases such as amyotrophic lateral sclerosis, Duchene muscular atrophy, spinocerebellar degeneration, multiple system atrophy, Parkinson's disease, and multiple sclerosis are examples of this.

    Neurological illnesses that are rare and difficult to treat may be hereditary, post- infectious, iatrogenic, or of unknown cause. They may have an impact on the brain, spinal cord, or peripheral nerves. Mild tremors to substantial motor and cognitive impairment are common symptoms. Therapy is frequently helpful.


    How Does Neurology Work? 


    Neurology works with Neurosurgery, Cerebrovascular Medicine, and Rehabilitation to offer medical care. For example, if we identify a patient with an acute stroke in our department, we promptly refer the patient to a stroke treatment team at our hospital and begin proper therapy.

    Patients who come to us for outpatient dementia exams frequently have neurosurgical diseases such as persistent subdural hematomas or brain tumors. In such instances, Neurosurgery takes over treatment immediately. 


    What is Rare & Intractable Neurological Disease?

    Intractable Neurological Disease

    Any disease of the nervous system that is intractable is referred to as an intractable neurological disorder. Structural, metabolic, or electrical abnormalities in the brain, spinal cord, or other nerves can cause a variety of symptoms that are difficult to detect and treat. Paralysis, muscle weakness, poor coordination, loss of feeling, convulsions, disorientation, pain, and altered states of awareness are some of the symptoms. 

    There are several documented neurological disorders, some of which are reasonably common but many of which are extremely unusual. They can be evaluated neurologically and investigated and treated in the fields of neurology and clinical neuropsychology.

    Preventive measures, lifestyle modifications, physiotherapy or other treatment, neurorehabilitation, pain management, medicines, procedures performed by neurosurgeons, or a specialized diet are all examples of interventions for neurological disorders.


    Types of Rare & Intractable Diseases

    Types of Rare & Intractable Diseases

    Neurological diseases are rare diseases with inadequate diagnosis and therapies. These conditions affect the neurological system, which includes the brain, spinal cord, and all of the nerves that run throughout the body. 

    Amyotrophic lateral sclerosis (ALS), Duchenne muscular dystrophy, and Huntington's disease are examples of uncommon neurological diseases. Creutzfeldt-Jakob disease (CJD) is a deadly, uncommon brain condition. It affects around one person in every million people globally each year, with approximately 350 cases reported in the United States each year.

    • Duchenne muscular dystrophy.
    • Normal pressure hydrocephalus.
    • Frontotemporal dementia.
    • Amyotrophic lateral sclerosis.
    • Creutzfeldt-Jakob disease.
    • Huntington’s disease.


    Duchenne Muscular Dystrophy (DMD)

    Duchenne Muscular Dystrophy (DMD)

    What Is Duchenne Muscular Dystrophy?

    Duchenne muscular dystrophy (DMD) is a hereditary disorder characterized by progressive muscle degeneration and weakening caused by changes in a protein called dystrophin, which aids in the maintenance of muscle cells. DMD is one of four types of dystrophino-pathies. 

    Becker Muscular Dystrophy (BMD, a mild form of DMD); an intermediate clinical presentation between DMD and BMD; and DMD-associated dilated cardiomyopathy (heart disease) with little or no clinical skeletal, or voluntary, muscle disease are the other three disorders in this category.

    DMD symptoms commonly appear in early childhood, between the ages of 2 and 3. The condition typically affects boys, but it can impact girls in rare cases.

    The prevalence of DMD is roughly 6 per 100,000 people in Europe and North America.


    DMD Symptoms

    The main sign of DMD is muscle weakness. It can start as early as age 2 or 3 and affect the proximal muscles (those closest to the centre of the body) first, then the distal limb muscles (those close to the extremities). 

    Lower external muscles are usually damaged before upper external muscles. Jumping, running, and walking may be challenging for the affected child. Other signs include calves hypertrophy, a waddling gait, and lumbar lordosis (an inward curve of the spine). 

    Later, the heart and breathing muscles are also impacted. Progression of weakness and scoliosis causes reduced pulmonary function, which can lead to abrupt respiratory failure.


    What Causes DMD?

    DMD has an X-linked recessive inheritance pattern and is passed on by the mother, who is referred to as a carrier. For more about the way gene mutations cause DMD,


    DMD Diagnosis

    If the doctor suspects DMD, he or she will perform additional testing, such as:

    • Blood tests. The doctor will take a blood sample from your kid and test it for creatine kinase, an enzyme released by injured muscles. A high CK level may indicate that your kid has DMD.
    • Gene testing.  Doctors can also examine the blood sample for alterations in the dystrophin gene, which causes DMD. Girls in the family can take the test to find out whether they have this gene.
    • Biopsy. The doctor uses a needle to extract a little bit of your child's muscle. They'll examine it under a microscope to search for low amounts of dystrophin, the protein that patients with DMD lack. 


    Normal Pressure Hydrocephalus (NPH)

    Normal Pressure Hydrocephalus

    What Is Normal Pressure Hydrocephalus?

    Normal pressure hydrocephalus (NPH) is a disorder characterized by an abnormal buildup of cerebrospinal fluid in your brain's ventricles (cavities or spaces). Cerebrospinal fluid (CSF) is a transparent liquid that flows around your brain and spinal cord, cushioning and protecting it. People with NPH have an excess of cerebrospinal fluid because their bodies are unable to drain and absorb the fluid appropriately. This fluid accumulation might be harmful to your brain.

    The distinction between NPH and other types of hydrocephalus is that even if there is more CSF than usual, the pressure inside the ventricles remains constant. This fluid accumulation causes symptoms to develop over time.


    What Causes Normal Pressure Hydrocephalus (NPH)?

    The exact cause of NPH isn’t clear. In most cases, the cause of the build-up of cerebrospinal fluid (CSF) is unknown. However, in some cases, NPH can occur as a result of other conditions that affect your brain, including:

    • Bleeding around your brain from head injuries or stroke.
    • Infections such as meningitis.


    Symptoms of Normal Pressure Hydrocephalus (NPH)

    There are three classic symptoms of normal pressure hydrocephalus:

    • Walking difficulty. This issue might be modest or severe. Many patients with NPH have difficulty getting back on their feet. Some say it feels like their feet are glued to the floor. This might result in a stumbling walk and difficulty climbing stairs and stepping over curbs. It also raises your chances of falling.
    • Dementia. Confusion, short-term memory loss/forgetfulness, difficulty paying attention, mood swings, and a lack of enthusiasm in everyday tasks are all common symptoms.
    • Bladder control issues. Urinary incontinence (the inability to retain urine), frequent urination, and a strong need to urinate are all problems.


    How Is Normal Pressure Hydrocephalus (NPH) Diagnosed?

    A detailed evaluation of symptoms and medical history, as well as a physical exam, are used to make a diagnosis. Among the other tests are:

    • Imaging tests. If necessary, your provider will arrange a CT scan or an MRI of your head to search for enlarged ventricles in your brain.
    • Cerebrospinal fluid testing. A spinal tap and external lumbar drainage are two of these tests. During a spinal tap, your doctor takes a tiny sample of cerebrospinal fluid and evaluates you to see whether your symptoms improve. During external lumbar drainage, they will remove additional cerebrospinal fluid using a specific catheter (tube) during a 36-hour period to examine if symptoms improve significantly and to investigate the possible benefit of implanting a shunt.
    • Evaluation of gait (walking). This is a walk test with a time limit. You are being monitored while you walk 10 meters (about 30 feet).
    • Neuropsychological evaluation. This entails a series of tests to detect whether there is a loss of brain function (including memory, concentration, and problem-solving) as a result of NPH.


    How Is NPH Treated?

    Although there is no treatment for NPH, the symptoms can be controlled with surgery. A shunt, or drainage system, is implanted during surgery. The shunt, a long, sturdy, flexible plastic tube, is inserted into one of your brain's ventricles. The other end is tunnelled beneath your skin to another region of your body, typically the lower abdomen.

    The shunt permits excess cerebrospinal fluid from your brain to drain and be absorbed back into your body. A shunt valve maintains the fluid flowing in the appropriate direction and at the right rate. The shunt will be implanted in your body for the remainder of your life. 


    Frontotemporal Dementia

    Frontotemporal Dementia

    Frontotemporal dementia refers to a spectrum of brain disorders that mostly affect the frontal and temporal lobes. These brain regions are commonly related with personality, conduct, and language.

    Parts of these lobes decrease in frontotemporal dementia (atrophy). The signs and symptoms differ according on whatever area of the brain is damaged. Some patients with frontotemporal dementia have major personality changes, becoming unsociable, impulsive, or emotionally indifferent, while others lose the capacity to use language appropriately.

    Frontotemporal dementia is sometimes misdiagnosed as a mental disorder or Alzheimer's disease. However, frontotemporal dementia occurs at an earlier age than Alzheimer's disease. Frontotemporal dementia is most common between the ages of 40 and 65, but it can develop at any age. FTD accounts for around 10% to 20% of all dementia cases.


    Frontotemporal Dementia Symptoms

    The signs and symptoms of frontotemporal dementia might vary from person to person. The signs and symptoms worsen with time, frequently over years.

    Clusters of symptom types are common, and individuals may experience more than one cluster of symptom types.

    Behavioral changes:

    The most common signs of frontotemporal dementia involve extreme changes in behavior and personality. These include:

    • Increasingly inappropriate social behavior.
    • Loss of empathy and other interpersonal skills, such as having sensitivity to another's feelings.
    • Lack of judgment.
    • Loss of inhibition.
    • Lack of interest (apathy), which can be mistaken for depression.
    • Repetitive compulsive behavior, such as tapping, clapping or smacking lips.
    • A decline in personal hygiene.
    • Changes in eating habits, usually overeating or developing a preference for sweets and carbohydrates.
    • Eating inedible objects.
    • Compulsively wanting to put things in the mouth.


    Speech& language problems:

    Language difficulties, speech impairment, or loss are all symptoms of frontotemporal dementia. Primary progressive aphasia, semantic dementia, and progressive non-fluent aphasia are all symptoms of frontotemporal dementia.

    These conditions can lead to the following issues:

    • Increasing difficulty utilizing and understanding written and spoken language, such as difficulty identifying the appropriate term to use in speaking or naming items.
    • Having difficulty naming items, potentially substituting a specific word with a more generic one such as "it" for pen.
    • Not knowing what words mean.
    • speaking with hesitation that may seem telegraphic.
    • Making grammatical errors in sentence building.


    Motor disorders:

    Rarer varieties of frontotemporal dementia are distinguished by movement difficulties comparable to those seen in Parkinson's disease or amyotrophic lateral sclerosis (ALS).

    Motor-related problems may include:

    • Tremor.
    • Rigidity.
    • Difficulty swallowing.
    • Muscle spasms or twitches.
    • Falls or walking problems.
    • Muscle weakness.
    • Poor coordination.
    • Inappropriate laughing or crying.


    Causes of Frontotemporal Dementia

    The frontal and temporal lobes of the brain deteriorate in frontotemporal dementia. Furthermore, some chemicals accumulate up in the brain. It is frequently unknown what causes these modifications.

    There are genetic mutations associated with frontotemporal dementia. However, more than half of persons with frontotemporal dementia have no family history of dementia.

    Recently, researchers discovered that frontotemporal dementia and amyotrophic lateral sclerosis share genetics and molecular mechanisms. However, further study is needed to determine the link between these disorders.


    Diagnosis of Frontotemporal Dementia

    There is no one test that can diagnose frontotemporal dementia. Doctors check for disease symptoms and try to rule out other probable causes. Because symptoms of frontotemporal dementia sometimes coincide with those of other conditions, early diagnosis can be particularly difficult.

    1. Blood tests. Your doctor may order blood tests to rule out other conditions, such as liver or renal disease.
    2. Sleep studies. Some obstructive sleep apnea symptoms (memory and cognitive impairments, as well as behavioral abnormalities) are comparable to those of frontotemporal dementia. If you also have sleep apnea symptoms (loud snoring and breathing pauses while sleeping), your doctor may order a sleep study to rule out obstructive sleep apnea as a cause of your symptoms.
    3. Neuropsychological testing. Doctors will sometimes put your thinking and memory abilities to the test. This form of testing is very useful in diagnosing the type of dementia earlier. The pattern of abnormal testing results may aid in differentiating frontotemporal dementia from other types of dementia.
    4. Magnetic resonance imaging (MRI).  MRI scan produces comprehensive pictures of the brain by using radio waves and a strong magnetic field.
    5. FDG-PET scan (fluorodeoxyglucose positron emission tracer). This test employs a low-level radioactive tracer that is injected into the blood. The tracer can assist identify parts of the brain where nutrients are poorly digested. Areas of poor metabolism can reveal where degeneration has occurred in the brain, assisting clinicians in diagnosing the kind of dementia.


    Frontotemporal Dementia Treatment

    Frontotemporal dementia presently has no cure or specific therapy. Drugs used to treat or reduce Alzheimer's disease do not appear to be useful for patients with frontotemporal dementia, and some may worsen symptoms. Certain drugs and speech therapy, on the other hand, can help control the symptoms of frontotemporal dementia.


    Creutzfeldt-Jakob Disease

    Creutzfeldt-Jakob disease (CJD) is a degenerative brain condition that eventually leads to death. Symptoms of Creutzfeldt-Jakob disease may resemble those of other dementia-like brain disorders, such as Alzheimer's disease. However, Creutzfeldt-Jakob disease normally advances much faster.

    CJD first gained public notice in the 1990s, when several persons in the United Kingdom contracted a type of the disease known as variant CJD (vCJD) after consuming meat from sick cattle. However, tainted beef has not been associated to "classic" Creutzfeldt-Jakob disease. All kinds of CJD are dangerous, although they are extremely rare. Every year, around one to two cases of CJD are identified per million individuals worldwide, with the majority of cases occurring in elderly adults.


    Creutzfeldt-Jakob Disease Symptoms

    Creutzfeldt-Jakob disease is marked by rapid mental deterioration, usually within a few months. Early signs and symptoms typically include:

    • Personality changes.
    • Memory loss.
    • Impaired thinking.
    • Blurred vision or blindness.
    • Insomnia.
    • Incoordination.
    • Difficulty speaking.
    • Difficulty swallowing.
    • Sudden, jerky movements.

    Mental symptoms develop as the condition advances. The majority of people ultimately go into a coma. The most common causes of mortality are heart failure, lung (respiratory) failure, pneumonia, or other infections, which usually occur within a year.

    Psychiatric symptoms may be more noticeable in persons with the rarer vCJD at first. Dementia, or the loss of the ability to think reason, and recall, often emerges later in the illness. vCJD also affects younger persons and appears to persist 12 to 14 months.


    Causes of Creutzfeldt-Jakob Disease

    Creutzfeldt-Jakob disease and its variants belong to a broad group of human and animal diseases known as transmissible spongiform encephalopathies (TSEs). The name derives from the spongy holes, visible under a microscope, that develops in affected brain tissue.

    The cause of Creutzfeldt-Jakob disease and other TSEs appears to be abnormal versions of a kind of protein called a prion. Normally these proteins are produced in our bodies and are harmless. But when they're misshapen, they become infectious and can harm normal biological processes.


    Creutzfeldt-Jakob Disease Diagnosis

    Only a brain biopsy or an autopsy examination of brain tissue after death can establish the existence of Creutzfeldt-Jakob disease (CJD). However, based on your medical and personal history, a neurological exam, and specific diagnostic tests, doctors may typically establish an accurate diagnosis.

    The examination is likely to uncover signs such as muscular twitching and spasms, aberrant reflexes, and coordination issues. People with may also experience blind spots and alterations in their visual-spatial perception.

    In addition, doctors commonly use these tests to help detect CJD:

    • Electroencephalogram (EEG). Using electrodes inserted on the scalp, this test monitors the electrical activity of the brain. People with vCJD have a distinctively aberrant pattern.
    • MRI. This imaging technique creates cross-sectional pictures of the head and body using radio waves and a magnetic field. Because of its high-resolution scans of the brain's white and gray matter, it's extremely valuable in identifying brain problems.
    • Spinal fluid analysis. The brain and spinal cord are surrounded and protected by cerebral spinal fluid. A lumbar puncture, often known as a spinal tap, is a test in which doctors use a needle to extract a small amount of this fluid for testing. This test is frequently used to rule out other neurological diseases, however, elevated levels of particular proteins found in the brain may suggest CJD or vCJD.


    Creutzfeldt-Jakob Disease Treatment

    Creutzfeldt-Jakob disease and its variations have no effective therapy. Many medications have been tested and found to be ineffective. As a result, doctors focus on treating pain and other symptoms and making patients as comfortable as possible. 


    Huntington's Disease

    Huntington's Disease

    Huntington's disease is a condition that causes sections of the brain to stop operating correctly over time. It is passed down (inherited) from one's parents.

    It worsens steadily over time and is frequently deadly after up to 20 years. 


    Huntington's Disease Signs & Symptoms

    The symptoms usually start at 30 to 50 years of age but can begin much earlier or later.

    Symptoms of Huntington's disease can include:

    • Difficulty concentrating and memory lapses.
    • Depression.
    • Stumbling and clumsiness.
    • Involuntary jerking or fidgety movements of the limbs and body.
    • Mood swings. 
    • Personality changes.
    • Problems swallowing, speaking, and breathing.
    • Difficulty moving.


    Huntington's Disease Treatment

    There's currently no cure for Huntington's disease or any way to stop it getting worse.

    But treatment and support can help reduce some of the problems it causes, such as:

    • Medicines for depression, mood swings, and involuntary movements.
    • Occupational therapy to help make everyday tasks easier.
    • Speech and language therapy for feeding and communication problems.
    • Physiotherapy to help with movement and balance.



    Intractable and rare diseases

    Most people associate neurological problems with a few diseases that impact millions of people, such as epilepsy, Parkinson's disease, and stroke. While many experts devote the majority of their efforts to these catastrophic diseases, they also have highly committed research programs devoted to developing treatments for a variety of rare diseases, which are classified as conditions affecting fewer than 200,000 Americans.

    Rare neurological disorders studied by NINDS-funded researchers and clinicians include amyotrophic lateral sclerosis (ALS), Duchenne muscular dystrophy, and Huntington's disease.