The Fahr's disease Is a pathology of inherited genetic origin associated with the development of cerebral calcifications (Polo Verbel, Torres Zambrano, Cabarcas Barbosa, Navas, González, Montoya and Bolaños García, 2011).
This disorder is characterized mainly by the presence of neurological and psychiatric alterations. Some of them are related to the deterioration of the mental functions, the motor alterations or the behavioral anomalies (Polo Verbel et al., 2011).
The specific causes of this disease are not known with accuracy (Pérez et al., 2012). Some authors, such as Oviedo Gamboa and Zegarra Santiesteban (2012), relate their etiology to a genetic anomaly located on chromosome 14. This produces bilateral and progressive calcification of various brain areas, especially the ganglia of the base and the cerebral cortex (Oviedo Gamboa And Zegarra Santiesteban, 2012).
The diagnosis of this neurodegenerative disorder is based mainly on the use of neuroimaging tests (Pérez Maciá, Martínez Cortés, Pecino Esquerdo, García Fernández, 2012).
Normally, the technique of choice is Computed axial tomography Without contrast (Pérez Maciá et al., 2012).
There is no cure for Fahr syndrome, nor a specific treatment (Lacoma Latre, Sánchez Lalana, Rubio Barlés, 2016).
Usually a symptomatic and rehabilitative medical approach is used. However, the prognosis of people with Fahr syndrome is unfavorable (Oviedo Gamboa and Zegarra Santiesteban, 2012).
It is a disease that produces a progressive and incapacitating deterioration (Oviedo Gamboa and Zegarra Santiesteban, 2012).
Characteristics of the Fahr's disease
Fahr's disease is a disorder of genetic origin, characterized by the presence of neurological and psychiatric disorders (National Institute of Neurological Disorders and Stroke, 2016).
It is a degenerative neurological disorder that will cause a systematic impairment of cognitive abilities, motor skills or behavior. In addition, it may be accompanied by other complications such as convulsive episodes (National Organization for Rare Disorders, 2016).
In the medical literature, a wide variety of terms are commonly used to refer to this disorder: primary familial cerebral calcification, cerebral ferrocalcinosis, Fahr syndrome, cerebro-vascular ferrocalcinosis, idiopathic cerebral calcification, etc. (National Organization for Rare Disorders, 2016).
The term Fahr syndrome is usually restricted to define a clinical picture whose etiology is not clearly defined or is associated with metabolic or autoimmune alterations (Oviedo Gamboa and Zegarra Santiesteban, 2012).
For its part, the term Fahr's disease is used to refer to the disorder caused by hereditary genetic origin (Oviedo Gamboa and Zegarra Santiesteban, 2012).
In both cases, signs and symptoms are associated with the presence of calcifications in different brain regions.
The importance of calcium
Calcium is a fundamental biochemical component in our body. Its functions encompass a broad field of influence: regulation of heart rate, production of hormones, control of blood clotting, regulation of muscle activity or brain activity (National Institutes of Health, 2015).
Our body is composed of a large amount of calcium, approximately 1000 g in adults (Gómez Giraldo, 2016). In addition, we have a wide variety of mechanisms that allow us to control its volume and distribution (American Society of Clinical Oncology, 2016).
Various pathological factors such as genetic abnormalities can alter their Hypercalcemia , Calcification of structures, etc.
By the term calcification we refer to an anomalous process that causes a pathological accumulation of calcium in any structure of our organism.
In the case of the brain, it is defined by the accumulation of calcium in the small arterial and venous blood vessels, as well as in the capillaries (Pamo-Reyna, Cumpa-Quiroz, Rosales-Mendoza, Cabellos-Gavidia, 2016).
This situation will produce an alteration of the blood flow and injuries of the nervous tissue, among other ailments. All these responsible for the development of the symptomatology of Fahr syndrome.
It usually affects the cortical and subcortical regions (Pamo-Reyna, Cumpa-Quiroz, Rosales-Mendoza, Cabellos-Gavidia, 2016).
The most affected areas being the ganglia of the base or Basal ganglia . This brain structure plays an essential role in the regulation and initiation of movement (Neurowikia, 2016).
An abnormal deposit of iron, aluminum, zinc or magnesium may also be detected (Pamo-Reyna et al., 2016).
The specific mechanism by which an accumulation of this substance occurs is not yet known. Some authors like Oviedo Gamboa and Zegarra Sanesteban (2012), suggest some hypotheses:
- Anomaly in intra and extra cellular calcium concentrations.
- Anomaly in concentrations of phosphate .
- Anomaly in the Blood brain barrier .
- Reduction of blood flow in different brain areas.
In 1850 several neurological abnormalities related to Fahar's syndrome began to be identified (Polo Verbel et al., 2011).
It was Delacour who described the presence of vascular calcifications in areas of the basal ganglia associated with neurological symptoms in a 56-year-old patient (Polo Verbel et al., 2011).
In subsequent years, other researchers such as Bamberger described clinical findings through histopathological analyzes of brain calcifications (Polo Verbel et al., 2011).
It referred to the presence of calcifications in the small cerebral blood vessels associated with a medical history of Epileptic episodes Y Intellectual disability (Polo Verbel et al., 2011).
It was not until 1930 when Theodor Fahr referred to this medical picture as an independent clinical entity, described as Fahr's disease (Pamo-Reyna et al., 2016).
Is it a frequent pathology?
Fahr's disease is a rare neurological disorder in the general population (Saleem et al., 2013). It is often classified within rare diseases.
Epidemiological analyzes associate its incidence to a figure below 1 case per million people worldwide (Saleem et al., 2013).
Normally, its prevalence tends to increase with increasing age (Carrillo, Álvarez de Sotomayor, Lucena, Castro and Izquierdo, 2006).
The typical onset of this disease is between the third and fifth decade of life (Cassiani et al., 2015).
In addition, two peaks of maximum incidence have been identified (Pérez Maciá et al., 2012):
- Beginning of the adult stage : There is a symptomatology characterized by psychiatric disorders.
- From 50-60 years of age : E presents a symptomatology characterized by the Cognitive impairment And psychomotor alterations. Psychiatric symptoms, especially affective disorders, are also present at this stage.
Signs and symptoms
Fahr's disease is fundamentally defined by the presence and development of neurological and psychiatric disorders (Saleem et al., 2013).
Here are some of the most common:
Neurological disorders
- Muscle hypo / hypertonia : Muscle tone is altered in most cases. Significant sagging or stiffness may occur. Voluntary and involuntary movements are often severely reduced.
- Tremor We can identify the presence of a constant and rhythmic involuntary movement. It usually affects the head, arms and hands.
- Parkinsonism Tremors and other symptoms may develop into a clinical picture similar to Parkinson's. The most common characteristics are rest tremor, absence of voluntary movement, muscular rigidity, posture instability, etc.
- Spastic paralysis : The different muscle groups achieve a very high muscle tone that prevents the realization of any type of movement. This type of paralysis may lead to the development of monoparesis / monoplegia, hemiparesis / hemiplegia, diparesia / diplegia, tetraparesia / tetrapegia.
- Athetic paralysis: Muscle tone tends to fluctuate persistently resulting in the development of involuntary movements and / or primitive reflexes.
- Motor apraxias Presence of marked difficulty or inability to perform motor activities related to a previous planning process (sequences, goal / goal, instruction, etc.).
- Convulsive crisis : It is frequent the development of episodes of muscle spasms and contractions or motor agitation associated with an abnormal and synchronous neuronal activity. There may also be episodes of temporary loss of consciousness or perception of abnormal perceptual sensations (light stimuli, tingling, etc.).
- Cognitive deficit : The most characteristic feature of patients affected by Fahr syndrome is the progressive deterioration of mental abilities. The most common is to observe an attentional commitment, reduction of processing speed, space-time disorientation or memory problems. Normally, this table is referred to as a pseudodemential process.
- Disorders of speech : Patients begin with difficulty in maintaining the thread of a conversation, finding the right words or articulating the language. These types of anomalies may progress towards partial or total communicative isolation.
Psychiatric Disorders
- Behavioral disorders: Patterns of altered behavior tend to appear. These are characterized mainly by the presence of repetitive activities and stereotyped behaviors. The people affected usually do the same type of activities persistently. In addition, they present incoherent or inappropriate behavior to contextual situations.
- Personality changes The person's personality traits are often distorted and Emotional lability , Irritability, lack of initiative, demotivation, social isolation, anxiety.
- Psychosis There is a significant loss of contact with reality. Obsessions, false beliefs, delusions or hallucinations are often observed.
- Turmoil crisis : Episodes of aggressiveness, motor agitation, restlessness, nervousness, disorganized speech or euphoria may develop.
- Depression : Some or all of the symptoms related to depressive disorder such as hopelessness, sadness, irritability, loss of interest, constant fatigue, difficulty concentrating, sleep disorders, thoughts of death, headache, etc. may appear.
Causes
Authors such as Lacoma Latre, Sánchez Lalana and Rubio Barlés (2016) define Fahr's disease as a syndrome of unknown or unknown etiology that is associated with the development of bilateral calcifications in different brain regions.
However, others such as Cassani-Miranda, Herazo-Bustos, Cabrera-González, Cadena-Ramos and Barrios Ayola (2015), refer to a hereditary genetic origin that occurs without the incidence of other infectious, traumatic, Biochemical or systemic.
Its origin is related to a genetic alteration located on chromosome 14 (Oviedo Gamboa and Zegarra Santiesteban, 2012) and associated to gene SLC20A2 (Genetics Home Reference, 2016).
This gene is primarily responsible for providing biochemical instructions for the manufacture of a type of protein. It plays an essential role in the organic regulation of phosphate levels, among other functions (Genetics Home Reference, 2016).
Some clinical studies, such as Wang et al. (2012), have associated mutations in the SLC20A2 gene and the clinical course of Fahr syndrome in several families (National Organization for Rare Disorders, 2016).
In addition, other genetic abnormalities related to Fahr syndrome have been identified: mutations in the PDGF gene and PDGFRB (National Organization for Rare Disorders, 2016).
Diagnosis
The diagnosis of Fahr's disease requires the combination of a neurological and psychiatric examination.
In the case of neurological examination, the fundamental intervention is based on the realization of a Computed tomography (Pérez Maciá et al., 2012).
This type of neuroimaging technique allows us to identify the presence and location of cerebral calcifications (Pérez Maciá et al., 2012).
It is essential to perform a neuropsychological evaluation to specify the entire spectrum of cognitive and psychomotor abnormalities and abnormalities.
The type of neuropsychological testing that can be undertaken is broad, usually depending on the choice of the professional. Some of the most used are: Wechler Intelligence Scale for Adults (WAIS), King's Complete Figure, Stroop Test, TMT Trace Test, etc. (Cassani-Miranda et al., 2015).
In addition, all this evaluation is accompanied by a psychological and psychiatric assessment for the identification of mood-related alterations, perception of reality, patterns of behavior, etc.
Treatment
As we pointed out in the initial description, there is still no cure for Fahr's syndrome (Lacoma Latre, Sánchez Lalana, Rubio Barlés, 2016).
Basic medical interventions are directed towards the treatment of symptoms and medical complications: pharmacological treatment of seizures, Cognitive rehabilitation Impairment of mental abilities or physical rehabilitation of motor complications.
Although there are experimental therapies, they do not usually report significant benefits.
What is the medical condition of the affected persons?
Cognitive, physical and functional impairment is exponential. This disease usually progresses towards total dependence and the inevitable demise of the affected person.
References
- ADCO. (2016). Hypercalcemia . Retrieved from the American Society of Clinical Oncology.
- Carrillo, R., Álvarez de Sotomayor, J., Lucena, C., Castro, D., & Izquierdo, G. (2006). Fahr disease and gestation. Clin Invest Gin Obst .
- Cossani-Miranda, C., Herazo-Bustos, M., Cabrera-González, A., Cadena-Ramos, I., & Barrios-Ayola, F. (2015). Psychosis associated with Fahr syndrome: report of a case. Rev Colom Psiquiat .
- Gómez Giraldo, C. (2016). Hypercalcemoa and Hypocalcemia.
- Lacoma Latre, E., Sánchez Lalana, E., & Rubio Barlés, P. (2016). Fahr disease. Diagnostics .
- NIH. (2016). Fahr's Syndrome . Retrieved from the National Institute of Neurological Disorders and Stroke.
- NIH. (2016). SLC20A2 . Retrieved from the Genetics Home Reference.
- NORD. (2016). Primary Familial Brain Calcification . Retrieved from the National Organization for Rare Disorders.
- Oviedo Gamboa, I., & Zegarra Santiesteban, W. (2012). Tomographic characteristics in a patient with Fahr syndrome, on the subject of a case. Gac Med Bol .
- Pamo-Ryna, O., Cumpa-Quiroz, R., Rosales-Mendoza, K., & Cabellos-Gavidia, D. (2016). Fahr disease. Photo Clinic .
- Pérez Maciá, V., Martínez Cortés, M., Pecino Esquerdo, B., & García Fernández, L. (2012). Atypical presentation of psychiatric symptoms: Fahr's disease. Psiq Biol .
- Acknowledgments REFERENCES Acknowledgments REFERENCES Acknowledgments REFERENCES Acknowledgments REFERENCES [1] Fahr disease is an uncommon cause of brain calcifications. Acta Neurol Colomb .
- Saleem et al. (2013). Fahr's syndrome: literature review of current evidence. Orphanet Journal of Rare Diseases .