Learning is a constant part of human behavior throughout life, but the quantity and quality of knowledge acquired during the first year of life is far greater—or at least comparable—to that acquired over the rest of a lifetime. The human brain increases in weight by one gram per day during the first year, followed by the formation of neuronal connections and networks that enable social smiling at one month of age, recognition of unfamiliar people at seven months, and learning to refuse to release objects around one year of age. In parallel, motor development progresses, allowing children to walk between 12 and 16 months. As development continues, cognitive (learning) and behavioral (approach–avoidance) growth intertwine, along with social interactions with parents and siblings. Many times, it is the parents—and sometimes pediatricians—who first notice that a child seems “different” or shows behaviors that draw attention.

Symptoms

The spectrum of cognitive-behavioral disorders is very broad, as are their symptoms. In general, symptoms include not achieving cognitive or behavioral milestones within the age range considered normal. For example, not exhibiting a social smile by the second month of life or not recognizing strangers by twelve months. Cognitive-behavioral disorders often form part of a broader condition, frequently with a genetic basis that may also affect other organs.

Who is affected?

The incidence of cognitive-behavioral disorders is estimated to be between 1% and 3% of all children.

Diagnosis

Parents are often the first to notice atypical signs in development or behavior, sometimes by comparing with siblings. During routine visits, the pediatrician evaluates age-appropriate developmental skills. If further assessment is needed, pediatric neurologists and geneticists can provide a more precise diagnosis. Diagnostic tests for these disorders always include a physical examination, genetic analysis, and laboratory tests that evaluate for metabolic diseases. Neuroimaging studies may also be helpful.

Common treatments

Treatment depends on the cause of the cognitive-behavioral developmental disorder. If the cause is metabolic, effective and sometimes curative treatments may exist. If the cause is genetic, it is possible to predict the course of the condition and recommend supportive educational strategies, although fully effective treatments are not yet available.

The physical examination helps determine whether the child is reaching developmental milestones appropriate for their age.

Genetic tests detect whether there is an alteration in the patient’s genes that could explain the observed anomaly.

Laboratory tests—typically using blood or urine—help confirm or rule out abnormalities in the body’s normal metabolic pathways.

Most common tests

Pediatric neurological examination, imaging studies, metabolic laboratory tests, genetic studies based on sequencing or ultra-sequencing, and evaluation by Child Psychiatry (Pediatric Psychiatry).

Prevention

If there is a family history of cognitive-behavioral disorders, genetic counseling prior to pregnancy may be useful. The neurosensory development of children is a complex process that begins during intrauterine life and continues from the neonatal stage through childhood and adolescence. Adequate monitoring during pregnancy and childbirth is also essential to help prevent these types of disorders.

HSPs are considered rare diseases, with symptoms that may begin from childhood to adulthood, depending on the genetic type. Neurologically, the primary problem is a progressive degeneration or dysfunction of the nerve pathways that run from the brain to the spinal cord, which are responsible for controlling limb movement and mainly affect the legs.

There are different forms of HSPs, sometimes classified as “pure” and “complex” types. In the pure forms, the symptoms are mainly limited to difficulty walking due to stiffness in the lower limbs. In the complex forms, in addition to paraparesis, other neurological symptoms or involvement of other organs may occur. To date, more than 80 genes have been identified in which mutations can cause HSPs. This explains the variability within HSPs, although each genetic type may present differently in each patient or family.

Although HSPs share the characteristic of leg spasticity with cerebral palsy, they are a distinct condition. In HSPs, there is no fixed brain injury present at birth, but rather a genetic alteration that causes a slow and progressive development of symptoms, which can sometimes be difficult to detect.

Symptoms

The main symptom of HSPs is progressive difficulty walking, caused by a combination of muscle weakness and spasticity in the legs. The most common signs and symptoms are:

• Gait disturbances.
• Spasticity and increased reflexes.
• Muscle weakness, predominantly in the legs.
• In more severe cases, involvement of the arms.
• Sphincter control is preserved in most cases, although urinary or bowel difficulties may occur.
• Additional neurological symptoms in complex forms (such as ataxia, visual or auditory disturbances, epilepsy, cognitive impairment, etc.).

Who is affected by the condition?

HSPs can affect people of any age, although symptoms usually begin in childhood or adolescence. Both men and women can be affected by the condition.

Diagnosis

Diagnosis involves several tests, which you can find here, and include:

• Clinical history and neurological examination.
• Brain and spinal magnetic resonance to rule out other causes.
• Molecular genetic testing to confirm the causative mutation.
• Neurophysiological or ophthalmological assessments.

At Vall d’Hebron University Hospital, patients benefit from the most advanced genetic sequencing techniques to achieve a precise molecular diagnosis quickly and efficiently. However, a proportion of patients still remain undiagnosed. That is why we are engaged in research to try to diagnose all cases and participate in international registries and projects aimed at improving the clinical assessment of patients.

You can view the HSP diagnosis infographic here.

Typical treatment

Monitoring of the disease includes:

• Regular assessment of clinical progression using specific scales. In addition, there are clinical scales for children before adolescence.
• Involvement of a multidisciplinary team, with Rehabilitation and Orthopaedic Surgery as key collaborators.
• Psychological and social support.
• Health education and adaptation to daily activities.

Currently, there is no cure, but multiple treatments are available to improve symptoms and quality of life:

• Physiotherapy and rehabilitation.
• Targeted botulinum toxin injections into the most affected muscles.
• Pharmacological treatment with oral muscle relaxants (baclofen, tizanidine, etc.) or other medications to manage symptoms.
• Orthoses and assistive devices.
• Advanced surgical treatments such as intrathecal baclofen pump implantation or selective dorsal rhizotomy.

The hospital offers cutting-edge surgical techniques and access to clinical trial units, enabling patients with HSPs to benefit from experimental therapies and innovative treatments.

HSPs can present at different stages of life and are chronic conditions that require long-term monitoring. At Vall d’Hebron Hospital, lifelong follow-up is ensured from the prenatal period through to adulthood. We also collaborate in research and ensure a smooth and effective transition through joint consultations and efficient communication. We also collaborate with patient associations to support research and raise public awareness about these conditions.

Discover more about the disease in this video:

A headache is not a disease but a symptom of other diseases, usually neurological or alterations of cranial structures (musculature, bones, dental pieces, paranasal sinuses, etc.), they cause an activation of pain receptors that depend on the trigeminal nerve or the first cervical nerve roots.

The causes of headache are multiple, from diseases to trivial factors (such as headache attributed to a rhinosinusitis or the consumption of substances such as alcohol), from diseases that cause recurrent headaches (such as migraine or neuralgia) to serious illnesses that can put the life of the person at risk (such as cerebral haemorrhage or meningitis).

Although the vast majority of people will present occasional and mild headaches, in some cases, the same headache and the rest of the symptoms of the diseases that cause it can interfere seriously in their usual daily life activities, generating disability and a significant decrease in quality of life. This combination of high prevalence, along with the great diversity of causes, some of them potentially disabling, makes the assessment of patients with headache a clinical challenge.

Symptoms

Headache is defined as presenting pain in any area of the head or face. When evaluating a person who has a headache it is important to specify the characteristics of the pain, these include:

• Location: Hemicranial (half-head), holocranial (whole head), frontal, temporal, occipital, facial, etc.
• Character: stabbing, oppressive, pulsating or beating, burning, electrical etc.
• Severity: Mild, moderate, intense, very intense.
• Duration of the episodes: Seconds, minutes, hours, days, constant.
• Form of onset and evolution.
• Frequency and timing of episode appearance.
• Factors that improve or worsen pain, like certain postures or manoeuvres such as cervical movements, tactile stimuli at certain points, eating, speaking or brushing the teeth.

In addition to the characteristics of pain, it is especially important to know what other symptoms accompany pain, since they give us a lot of information about the possible causes of a headache:

• Fever or cervical stiffness may indicate infections of the nervous system.
• Neurological symptoms such as loss of vision, strength or sensitivity or sudden speech disturbances may indicate brain diseases such as stroke or migraine.
• Sensitivity to stimuli such as light, noise or smells are common in migraine.
• Nausea or vomiting is common in migraine, but may also appear in patients with brain injury or hydrocephalus.
• Teary eyes, a runny nose or red eyes during pain are typical of trigemino-autonomous headaches such as cluster headaches.

Who is affected by the condition?

Most people will have a headache at some point in their life, and it is a symptom that can present at any stage from childhood to old age. Migraine and tension headaches are the most common causes of headache and particularly affect women aged between 15 and 55, being the third leading cause of disability in young adults (under 50 years of age).

Children and adolescents may also have headaches. Children have the same types of headaches as adults, but their symptoms can be a bit different, which can make it difficult to identify the type of headache.

Diagnosis

Headaches are divided into 3 groups:

• Primary headaches: They are diseases in which their main symptom is headache, which is recurrent. Examples include migraine, tension headache or trigeminal-autonomous headaches. It is the most frequent cause of headache, and usually there are no alterations in routine tests.
• Secondary headaches: Caused by other diseases that cause headache among other symptoms. Examples include headache attributed to cranial trauma, cerebrovascular diseases such as ischemic or haemorrhagic stroke, problems with cerebrospinal fluid pressure or the effects of substances or drugs.
• Neuralgia or painful neuropathies: Such as trigeminal neuralgia, which occur due to lesions in the cranial nerves.

For most people who have headaches, especially those who have presented several episodes throughout their lives, the diagnosis will be made through clinical interview and physical exploration and, most of the time, will not require any tests. The way the episodes of headache present is the key to being able to make the correct diagnosis.

When faced with a first episode of headache, especially if it is sudden or accompanied by alarm signs (e.g. fever, cervical stiffness or neurological symptoms) it will be necessary to rule out that it is a serious secondary headache. In these cases it will be especially important to perform blood tests, cerebrospinal fluid and brain imaging tests such as CT scans or magnetic resonance imaging.

Typical treatment

There are two types of treatment: Treatment of pain is usually performed with analgesic or anti-inflammatory drugs that will be adjusted according to the patient's response or tolerance. In addition, in cases of secondary headache it will be important to treat the cause. It is important to know that in the case of frequent headaches, understood as several days a month, the frequent use of painkillers can be harmful and the frequency must be evaluated with calendars in order to initiate preventive treatments, which aim to decrease the frequency and intensity of frequent headaches.

Typical tests

Most of the information required for diagnosis is obtained from clinical interview and physical examination, and thus most patients with headache, especially those who exhibit long-evolution headache episodes, will not need specific supplementary tests for diagnosis. The need for complementary explorations such as blood tests, cerebral or spinal neuroimaging (CT or MRI), lumbar puncture for cerebrospinal fluid tests or vascular tests are indicated in patients who present "alarm signs" that include:

• Sudden onset.
• Progressive worsening.
• Start during gestation or postpartum.
• Onset in people over 50.
• Alteration of the level of consciousness or neurological symptoms.
• Associated with symptoms such as fever, cervical stiffness, weight loss.
• Associated with systemic diseases (cancer, HIV infection, systemic infection, coagulation disorders).
• Triggered by postural changes.
• Triggered by cough or physical activity.
• Papilledema (alteration to the fundus of the eye).

Prevention

Preventive strategies will be especially important in people with recurrent headaches such as migraine or tension headache, in order to minimize the factors that can make the headaches appear more frequently. It is especially important to have regular routines, perform correct sleep hygiene and regular exercise. These measures will also be important to prevent overloading of the cervical or cranial musculature; or strategies to minimize stress and mood disorders.

What is DNA?

Our DNA is like a great library that contains all the information that makes our body work. Each of the books on the shelves are our genes, and an error in one of them is called mutation. These mutations cause genes to not be read correctly, and alter the manufacture of proteins and, therefore, also some functions of our body, leading to different diseases.

Our body is protected from these genetic disorders by having duplicate DNA, that is, we all have two copies of each gene, one inherited from our father and the other from our mother. This means that the appearance of genetic disorders is conditioned by the number of copies we have altered.

• Dominant expressions: This pattern occurs when a mutation in a single copy is sufficient to express the disease. For example, when the father is affected by the disease and the mother is not. In this case half of their children will be affected and the other half will not.
• Recessive expression: In this case, it is necessary for both copies of a gene to be altered for the disease to occur, that is, the mother and the father's copy must have the mutation. This means the father and mother will be carriers of the disease, and as a result, 25% of their children will be affected by the disease, 50% will be carriers and the other 25% will not be affected at all.
• Expression linked to the X chromosome: This chromosome determines the sex of living beings. Female people have two X chromosomes and those of male sex have an X and Y, becoming more vulnerable to mutations because they have only one copy. Diseases caused by mutations in the X chromosome can follow a dominant or recessive pattern:
  • In the dominant pattern, for example, if the father is affected and the mother is not, the women will be affected and the men will not. And should the mother be affected and the father is not, half of the children will be affected and the other half will not.
  • In the recessive pattern, if the father is affected by the disease and the mother is not, the women will be carriers and the men will not be affected. And should the mother be a carrier and the father be unaffected, half of the children will not be affected, half of the males will be affected and half of the women will be carriers.
• Mitochondrial expression: This happens when there are alterations in a small proportion of the DNA found in the mitochondria of the cell, that is, mitochondrial DNA. It is a particular pattern, since mitochondria are inherited solely from the mother and, therefore, only women can transmit the mutation. For example, if the father has affected mitochondrial DNA and the mother does not, no child will be affected. And if the mother is affected, but the father is not, all children will be more or less affected depending on the number of damaged mitochondria.
• De novo mutations: Sometimes mutations occur spontaneously in the affected child and are absent in the DNA of both parents. However, this mutation can be transmitted if the affected child has future offspring. In fact, all mutations inherited from parents were, at some point, de novo, and spontaneously appeared in a family ancestor.

Are there other factors that manifest a genetic disorder?

In addition to the main hereditary types, there are cases that do not follow these basic rules. This is due to the existence of other less known factors that make each person manifest the disease in different ways:

• Penetrance: This is defined as the proportion of individuals with a mutation presenting the disease. Therefore, there are genes that present 'incomplete penetrance', that is, not all individuals manifest the symptoms of the disease.
• Mosaicism: This phenomenon occurs due to a mutation that appears very early in the development of the foetus and causes not all cells in the body to contain the mutation. Thus, expression of the disease will vary depending on the type of cells affected.
• Genetic impression or imprinting: This is a genetic phenomenon through which the expression of certain genes is conditioned by the sex of the parent from which it was inherited. For example, in the case of myoclonic dystonia, the copy of the inherited gene from the mother is silenced. In this way, a person who has a mutation in the maternal copy of the gene will not show symptoms of the disease, although they will be a carrier and can transmit it to their offspring.

How is a genetic disorder diagnosed?

In recent years, the study of genetic mutations has evolved exponentially, thanks to the appearance of improved techniques that allow us to sequence our genome, all our DNA. Sequencing is basically 'reading' and knowing the exact sequence each of our genes has. Therefore, depending on the situation, we will analyse a specific gene or we will have to go further and read larger areas of the genome. That is why we have several strategies:

• Array-CGH analysis: This technique allows us to review some library shelves and check if a book is missing. Sometimes, neurological diseases may be due to the fact that several whole genes are missing, that is, several books in the library.
• Complete exome analysis: When we carry out this analysis, we read all the books in the library to look for spelling mistakes in one of the 8,000 genes we know can cause a genetic disorder.
• Complete genome analysis: There are times when we cannot find any errors in the books and we must review the other elements in the library such as bookshelves, furniture, etc. In our genome, in addition to genes, there are regions that act as spacers, regulators, and many other sequences with yet unknown functions, that could have an important impact on our body and that we must take into account.

The appearance and implementation of all these clinical techniques has led to giant leaps in the genetic diagnosis of many diseases, including dystonia and other movement disorders.

What is the treatment for a genetic disorder?

When we talk about genetic diseases we must be aware that the alteration is present in all the cells of our body and cannot be eliminated. New gene therapies focused on correcting the genetic error in some neurological diseases have been in development over the last few years.