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Differential diagnosis of cerebral palsies with some neurogenetic pathologies

Autor: Mariana Sprincean Nineli Revenco Ludmila Eţco Cornelia Calcîi Nadejda Lupuşor Svetlana Hadjiu
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In the article are analyzed aspects of differential diagnosis of cerebral palsies (CP) with neurogenetic pathologies such as Strumpell familial spastic paraplegia, spinal amyotrophy, progressive muscular dystrophies, hereditary diseases of amino acid metabolism, hereditary disorders of lipid metabolism, phacomatosis, Friedreih ataxia, myopathies, etc.

Differential diagnosis of CP with other diseases is difficult, especially in the younger age, because neurological pathologies of various etiologies and various pathogenetic aspects are presenting with similar clinical manifestations. Some CP clinical manifestations, especially motorial disorders, can be traced to hereditary and congenital pathologies, central nervous system developmental anomalies, hereditary neuro-muscular pathologies, etc. In order to establish a correct diagnosis, it is necessary to perform a correct and complete clinical and genealogical examination, to evaluate various methods of paraclinical investigation, as well as the medical-genetic counselling of the families of sick children.

Conclusion. The differential diagnosis of cerebral palsy with some neurogenic pathologies, especially during the recent development of the medical sci- ence complex, is set to be an extremely important subject of concern for contemporary society in general, in its continuous effort to provide sustainable growth. Development of child with CP and neurological disorders in early age depends largely on the multisystemic impairment, especially of the CNS (central nervous system). The multiple theoretical and methodological aspects of the CP, differential diagnosis and the neurogenic pathologies in children are mainly designed in terms of basic notions, and it’s elucidation and specification require further research on the efficiency of the application of resources to improve and correct the development of such children, in their early age.

Key words: cerebral palsy (CP), differential diagnosis, neurogenic pathologies, psycho-neurological development.

Differential diagnosis of cerebral palsy (CP) with other neuro-genetic diseases is difficult, especially in children of young age, because of various etiologies of neurological pathologies and different pathogenetic aspects, manifesting with similar clinical signs. Some clinical manifestations of the CP, particularly motor disorders, can be mentioned in patients with hereditary and congenital pathologies, in retardation of neuro-psychical development, in neuro-muscular hereditary pathologies, etc. In order to diagnose the pathologies correctly, it is necessary to make a comprehensive and correct analysis of the family, to evaluate different methods of clinical and paraclinical investigations, as well as methods of medico-genetic counseling of the families of affected children.

For the differential diagnosis of neuro-genetic pathologies it is necessary to take into account the character and evolution of the pregnancy and delivery of affected children, their health status in the neonatal period, psycho-motor development before the appearance of the first clinical manifestations, clinical polymorphism and features of the course of pathology. There are clinical signs in history of children with CP related to the complicated course of pregnancy, i. e., threat of spontaneous abortion, toxicosis, somatic, infectious disorders i. e., complicated delivery, long or rapid delivery activity, premature rupture of amniotic membranes, insufficiency of contractile activity, surgical interventions; fulminating, amniotic, salient forces of contraction, some surgery, etc.), asphyxia with signs of cerebral trauma. In the neonatal period in these children there are often revealed signs of global or focal neurological disorders, e. g., excitation or hypodynamy, tremor, disorders of muscle tone, Gräfe sign, increased cranial perimeter, abnormal stretch reflexes, seizures and autonomic disorders. In the history of children with congenital and hereditary diseases, as well as in children with neuro-muscular pathologies, usually there are no signs of pathological course of pregnancy and delivery. In few cases there can be noted some pathological signs, such as motor disorders in fetus, mild fetal asphyxia that parents do not note. Diagnosis of spastic forms of CP in infants does not pose any difficulties, manifesting with the following features: increased muscle tone, often accompanied by pathological tonic reflexes, often from the first months of life. In cases of decreased muscular tone in CP there are often difficulties in differential diagnosis with similar clinical syndromes caused by congenital and hereditary diseases. CP is characterized by stable development, stable status, without worsening over time, with the change of symptoms according to age. Simultaneously with the implementation of rehabilitation measures can be noted the signs of improvement of development of these children. In contrast, in children with neuro- genetic pathologies the evolution of the disease is slowly progressive and resistant to treatment.

We present here some criteria of differential diagnosis with neuro-genetic disorders:

Hereditary spastic paraplegia Strümpell caused by bilateral degenerative changes in pyramidal tract of posterior and lateral horns of the spinal cord. In few cases changes are noted at the level of the brainstem. In a lesser extent, cerebellar tracts are involved. On the background of lesion of pyramid tract develops gliosis. The vast majority of cases begin in the preschool period and adolescence, although in some patients clinical manifestations can start during the early years of life. Muscle weakness and motor disorders

progress gradually. Children walk in fingertips, and eventually develop clubfoot. The muscle tone in legs is increased. Legs stretch reflexes are exaggerated; clonus and pathologic plantar reflexes appears. Lower limbs are affected symmetrical, and the disturbances of sensitivity are not characteristic. Muscular atrophy is not characteristic, although sometimes a slight thickening of the lower limbs is noted [2]. The evolution of the disease is slowly progressive, in some cases, spasticity spreads over the thorax and upper limbs. Among other specific symptoms of the disease are: nystagmus, bulbar syndrome, ataxia, mental retardation. Common symptom in diplegic form of CP and spastic paraplegia Strümpell is spastic paraplegia in legs. But in Strümpell disease motor disorders may occur in more late stages of children development, after the child start to sit, to stand up and, occasionally, to walk, while in CP motor disorders manifested at birth.

Hereditary diseases of the neuro-muscular system manifesting with hypotonia must be differentiated from hypotonic to form of CP.

Spinal muscular atrophy or Werdnig–Hoffmann disease is caused by degenerative changes in the anterior horns of spinal cord, followed by secondary changes in the nerves, neuro-muscular synapses and muscles. The congenital form of this pathology is diagnosed at birth on the basis of signs of evident decreasing or absence of muscular tone, adopting of a frog-leg position. Spontaneous motor activity is evidently reduced. In this pathology there are only slight movements in hand fingers.Paresis of intercostal muscles leads to disorder of chest movements. Facial expressions are diminished. Stretch reflexes are abolished. In most cases the motor disorders remain without changes. Rarely, in late period, children can hold head and even can be placed in the sitting position with support. Usually, children are weak if standing, skills of walking virtually lacking. Children with congenital form die in early childhood due to complicating pathology. Psychic development in the case of spinal muscular atrophy is not affected at early stages, but later, develops a different degree of psychic retardation. In children with hypotonic form of CP decreasing of muscular tone is not so pronounced as in spinal muscular atrophy. Unlike the CP evolution of the spinal muscular atrophy is slowly progressive in the early form of spinal muscular atrophy, the children up to the age of 5 – 12 months develops deltoid muscles, abdominal muscles and muscles of the tongue. Can associate lumbar hyperlordosis and winged scapula (scapula alata).The process of atrophy can affect the myocardium, i. e., cardiomyopathy, with the development of acute heart failure, explaining the cause of the high lethality. Motor gastrointestinal disturbances can occur and changes in the bone tissue. Intellect is low. There is a correlation between the degree of impairment of muscles and mental retardation. In the final stage of muscle atrophy, the process spreads on the muscle of face, larynx and respiratory muscles.

Becker muscular dystrophy is a benign form of neuromuscular disease. The prevalence of this pathology is 1:20000 male newborns [3]. Becker muscular dystrophy can be diagnosed on the basis of presence of the characteristic signs, i. e., muscle cramps after exercise or decreasing of heart output. First clinical signs occur no earlier than in 10 to 15 years and the course of disease is milder. The capacity for work in patients is preserved. Intellect is normal, and heart disorders are absent. The level of creatine kinase is smaller than in DMD. Unlike DBD, in CP at the end of the first year of life on the background of decreased muscular tone occurs ataxia or hyperkinesia. An important aspect of differential diagnosis with CP is slow progressive evolution of the DBD.

Torsion dystonia or dystonia musculorum deformans (DMD) In children the most common form is the hyperkinetic type, characterized by involuntary movements of the muscles that maintain the posture. Another form of DMD is rigid, manifesting later although there are described types of pathology which begin in the early years of life. Rigid form of DMD is characterized by decreased dopamine synthesis and intensified catabolic processes, in the hyperkinetic type determined the increasing of synthesis of dopamine and epinephrine and intensifying its degradation. A therapeutic effect is noted in the administration of L-DOPA (Nakom), especially in rigid type of DMD (70 – 80% of patients), that confirms the presence of defect in catecholamine metabolism. It is difficult to make the differential diagnosis of CP and types of DMD in early stages. In the case of DMD, motor disorders appears usually on the background of normal development or in children with mild retardation of psycho-motor development, the evolution being slowly progressive, with a resistance to symptomatic treatment and rehabilitation measures, which is not characteristic

for the CP. The presence of similar cases in the family and aggravated family history suggests hereditary type of pathology. Improvement of clinical manifestations after administration of small doses of L-DOPA (Nakom) indicated the increased probability of DMD and decreased the probability of CP [8].

Phakomatoses are hereditary diseases characterized by multisystem disorders of the CNS, skin and sometimes internal organs.This group of diseases refers to exomesodermal dysplasia.In the early years of life CP needs to be differentiated from Ataxia-telangiectasia or Louis-Bar syndrome, with Neurofibromatosis or von Recklinghausen disease, and with Tuberous sclerosis or Bourneville’s disease. Clinical manifestations of the Ataxia-telangiectasia begin after the age of 3 to 5 years. But the literature describes cases of prime manifestations right from the first months of life. At the age of 7 to 12 months determined the retardation of motor development, characterized by disorders of coordination in seating, crawling, in support and walking. Muscle tone is reduced, voluntary movements of hands are uncoordinated. The infants with Louis- Bar syndrome often suffer from bronchial-pulmonary diseases caused by immunodeficiency status. When children start to walk, ataxia is becoming increasingly evident and the 1,5 – 2 years appears choreoathetosis, tremor, nystagmus, the saccade speech. At this stage clinical manifestation of Louis-Bar syndrome resemble those of atactic type of CP. Clinical manifestations noted in Ataxia-telangiectasia syndrome is completed by the vascular changes as ocular, oral mucosa, skin of chest and limbs.

On the skin of many patients can be observed pigmented “café au lait” spots and low pigmented regions. Unlike the CP the evolution is slowly progressive, and at the age of 8 to 9 years appear symptoms of impaired cerebral subcortical structures, muscular hypotonia converts to hypertonia, develops Parkinson-like syndrome, it becomes more obvious intellectual deficiency. The pneumoencephalography shows atrophy of cerebellum, and EEG findings suggests diffuse changes in brain bioelectrical activity. Diagnosis of Louis-Bar syndrome is confirmed by immunological analyses what confirm the deficiency of A and B immunoglobulins and other changes of immunological values.

Neurof ibromatosis or von Recklinghausen disease

In the early childhood similar to a CP one the following symptoms: muscular hypotonia and psycho-motor retardation. Neurofibromas on skin, on the line of the peripheral nerves, nerve plexi or cerebral is conferring specific clinical manifestations which differentiate neurofibromatosis from CP. In the case of neurofibromas located on the line of peripheral nerve, occur sensitivity disorders, flaccid paresis and paralysis of certain muscle groups. In the case of cerebral neurofibromas it leads to signs of focal and global brain disorders. Often neurofibromas locate in the region of sclera, cornea, lens, optic nerve. In neurofibromatosis are characteristic spots of increased pigmentation “café au lait” on the chest, abdomen, upper and lower limbs, which manifests at birth or may occur gradually over the first few years of life. With age, the number of increased pigmentation spots is increased. Sometimes other signs appear, such as: regions of decreased skin pigmentation, vascular spots, regions of hair with decreased pigmentation. Cerebellar neurofibromas lead to ataxia, neurofibromas in spinal cord can be manifested by flaccid or spastic paresis. Often it is found a mild mental retardation occurred long before the neurological manifestations [1].

Tuberous sclerosis or Bourneville’s disease is characterized by the triad of clinical manifestations: mental retardation, seizures and adenomatosis of sebaceous glands. The clinical picture usually manifests at the age of 4 to 5 years. In infants tuberous sclerosis resembles the CP by retardation of psycho- motor development and muscular hypotonia. During the development of the child, psychiatric disorders are aggravated, often convulsive syndrome is found. Adenomatosis of sebaceous glands in the facial region refers to the late symptoms of the disease, but pigmented or depigmented spots on the skin it is often can be observed even at birth or in early childhood. Tuberous sclerosis evolution is progressive, which is not characteristic for the CP.

The group of neuro-degenerative disorders includes Friedreich’s disease, Hereditary spastic paraplegia or Strumpell disease, Torsion dystonia or dystonia musculorum deformans etc [7].

Friedreich’s ataxia is caused by the degeneration of the posterior and lateral horns of the spinal cord. The pathological process involved spino-cerebellar tracts and, in less extent, pyramidal tract. Sometimes there are found changes of cerebellar and pontine nuclei and in the subcortical structures. Clinical manifestations usually appear at the age of 6 to 10 years. In some cases, motor development retardation appear during the early years of life. The children start to sit later, start to walk later with support; the movements are sloppy, often lose balance while walking and fall; muscle tone is decreased [1]. As the disease progress, ataxia becomes more expressed in the lower limbs and then in upper limbs; stretch reflexes are abolished initially at lower limbs, and then, at the upper limbs. Subsequently, with the involvement in the pathological process of pyramidal tract, decreasing of muscle tone sometimes change to increasing of muscle tone, in association with deep sensitivity disorders. Typical thoracic scoliosis of the spine and evident pes cavus deformity of the foot also known as the “Friedreich’s foot” are characteristic. In 80% of cases are found congenital heart defects and dystrophic myocarditis. Mental deficiency develops in 10 – 15% of patients on the background of evident neurological symptoms. There is a need for differentiation of Friedreich’s ataxia with atactic type of CP. Against the diagnosis of CP are the following signs: spinal signs of neurological disorders, spinal damage, characteristic deformity of the foot, as well as progressive evolution of pathology.

Hereditary diseases of amino acids metabolism (phenylketonuria, histidinemia, lysinemia, leucinosis) belongs to the hereditary enzymopathies caused by autosomal-recessive gene mutations. At the base of etiology of these pathologies is total or partial insufficiency of enzymes participating in the metabolism of one or other amino acid lead to synthesis of toxic metabolites which act toxic on nervous system. Parents of these children typically don’t  notice  any  disturbances  in  the  development of children in early periods of development, but sometimes can note in their children drowsiness, apathy, hypotonia, or, in contrast, hyperactivity, unmotivated cry, sleep disorders, which appear on the background of the problems with feeding or care.

As the child growth can be noted the retardation of psycho-motor development with major disorder of cognitive functions. The clinical picture is completed by other signs as: nystagmus, tremor of eyes, strabismus, seizures, tremor, increasing of stretch reflexes. Hydrocephalic or microcephalic syndrome can appear. Sometimes, the retardation of psychic development becomes evident only at the end of the first year of life. Changes in psychical development consist in apathy, diminishing of defense reactions, fatigue, and cognitive-verbal disorders. In some children it is found neurotic disorders, syndrome of excitation, aggressiveness, decreasing the motivation and motor disorders as muscle hypotonia and balance disorders. If the children are constantly acquiring new skills even in the most severe cases of CP, for the cases of hereditary disorders of the metabolism of amino acids is characteristic not just motor and mental retardation, but progressive and chronic worsening of the status. In case of suspicion of inborn errors of metabolism are administered special investigations assessing the concentration of amino acids in the urine and blood (hyperaminoaciduria and hyperaminoacidemia), as well as methods of assessing the levels of certain metabolites in biological fluids and tissues of the organism, as well as methods for assessing activity of enzymes [5].

Hereditary lipid metabolism disorders (gangliosidoses, leukodystrophy etc.) refers to group of the hereditary enzymopathies, in which the cells of the nervous system and other tissues of the body accumulates products of fat metabolism, leading to degenerative changes. The period of onset of clinical manifestations, severity of the process, evolution and course of disease are in direct correlation with metabolic and enzymatic defect. In most cases the clinical manifestations of damage of the nervous system appear only after a few months of age. In the first months of life these children develops in accordance with the standards, after which the child gradually loss the acquired skills.These manifestations parents can attribute to introducing certain foods in nutrition or infections or to immunization. In patients with gangliosidoses primarily affects mental and cognitive development and cognitive-verbal sphere, losing interest to environment, the children does not smile, develops speech pronunciation of sounds, suffer socio-affective behavior, are losing “awakening” reflex, not reacts to the mother’s voice, etc. Simultaneously develops muscle hypotony, child loses the ability to held the head, to turn from back to abdomen, to grab a toy, voluntary movements are rare, diminished. Over several months the hypotonicity transforms into hypertony, less pronounced compared to the CP and not associated with increasing of stretch reflexes. The symptoms described are associated with other neurological symptoms such as tremor, seizures, cranial nerve paresis (strabismus, ptosis, anisocoria, ophthalmoplegia). Leukodystrophies most commonly develops during pre-school period. Sometimes, however, the first clinical manifestations may occur in children of early age, which often creates difficulties in differential diagnosis of leukodystrophies with CP. Equally, as in gangliosidoses, patients with leukodystrophies develops normally in the first few months of life. Lately manifests neurological signs as following: apathy, adynamia or increased irritability, children become restless,crying for a long time,sucking difficulties, muscle tone diminished. Symptoms gradually worsen and appear new symptoms of the disease: increasing of head perimeter, associated signs of disorders of cranial nerve functions, i. e., strabismus, vertical and rotational nystagmus, optic nerve atrophy, bulbar syndrome, Gräfe sign, and seizures [10]. Hypotonicity gradually progress to rigidity until opisthotonus, hyperkineses are possible. Sometimes the disease manifested by convulsive syndrome. As neurological impairment is worsening, retention in the psycho-motor development also progresses. Other inborn error of metabolism, leukodystrophy, unlike the CP, is characterized by a progressive evolution and a severe retardation of psychical development, resistant to symptomatic treatment administered.

Mucopolysaccharidoses represents a group of disorders caused by defect of specific lysosomal hydroxylases that participates in the breakage of glycosaminoglycanes or mucopolysaccharides. Uncleaved material is deposited in virtually all body cells in lysosomes. Clinical manifestations are characterized by the impairment of nervous and skeletal-muscular system, eyes and internal organs. In the early childhood period, this group of diseases manifested with muscle hypotonia and psycho- motor retardation, and differential diagnosis is made with hypotonic form of CP. However, in children with mucopolysaccharidoses even from birth are noted some phenotypic characteristic features, i. e., macrocephaly, coarse facial features (prominent forehead, hypertelorism, small nose with flattened nose base, ears deformed, macroglossia), chest deformation, kyphosis, etc. Fingers and toes are short and wide, large abdomen, hepatomegaly and splenomegaly, often can be present umbilical and inguinal hernias. Heart pathology is manifested by cardiac arrhythmia, cardiac murmurs. Subsequently patients exhibits visual and hearing impairment, and sometimes develop cataracts or optic nerve atrophy. In children present a physical retardation. Mental deficiency is characteristic from mild to moderate or severe grade. The phenotype of children with CP, unlike that of patients with mucopolysaccharidoses, is usually normal, without the minor congenital anomalies or stigmas of abnormal embryogenesis. Diagnosis of mucopolysaccharidoses is confirmed by detection in urine of various fractions of glycosaminoglycanes, metachromatic substances, and accumulates in skin fibroblasts and leukocytes of mucopolysaccharides [9].

In neurogenetic pathologies can be determined different neurological manifestations on the presence of which we can make differentiation with cerebral palsy (Table I).


Differential diagnosis of cerebral paralysis with some neuro-genetic diseases, especially in the early period of development of the complex of health sciences, it a very important topic of concern for contemporary society in general, and need support to secure a sustainable and stable development.

Development of child suffered from CP with neuro-psychic disorders presenting in the first years of life, depends largely from the multi-systemic impairment and primarily to the CNS injury.

Multiple theoretical and methodological aspects of problems of differential diagnosis of CP and neuro- genetic pathologies are derived mainly from the basic definitions which need to be elucidated and clarified by following studies, using by application of resources of improvement and correction of development of affected children in the first years of life.


Differential diagnosis of cerebral paralysis with some neuro-genetic diseases, especially in the early period of development of the complex of health sciences, it a very important topic of concern for contemporary society in general, and need support to secure a sustainable and stable development.

Development of child suffered from CP with neuro-psychic disorders presenting in the first years of life, depends largely from the multi-systemic impairment and primarily to the CNS injury.

Multiple theoretical and methodological aspects of problems of differential diagnosis of CP and neuro- genetic pathologies are derived mainly from the basic definitions which need to be elucidated and clarified by following studies, using by application of resources of improvement and correction of development of affected children in the first years of life.

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