Benefits of robotic devices in medical rehabilitation of a case with neurofibromatosis type1

ANDRONIE-CIOARA Felicia Liana1, ȘEREȘ Daniela2, AVRAM GULER Natalia Loredana3,

CEVEI Iulia4, OPREA Claudia5, STOICANESCU Alexandra Maria4, JIMAN SCURT Laura Crina3,
GHERLE Anamaria3
Corresponding author: ȘEREȘ Daniela E-mail: [email protected]

Balneo Research Journal DOI: http://dx.doi.org/10.12680/balneo.2020.407 Vol.11, No.4, December 2020 p: 569–573

1 Department of Psychoneurosciences and Rehabilitation, Faculty of Medicine & Pharmacy, University of Oradea, Romania
2 Cluj Napoca County Emergency Hospital, Department of Neurology, Cluj-Napoca, Romania
3 Medical Rehabilitation Clinical Hospital Baile Felix, Romania
4 University of Medicine and Pharmacy “Victor Babes”, Timisoara, Romania
5 County Emergency Clinical Hospital Timisoara, Department of Pediatrics, Romania
Abstract
The term neurofibromatosis (NF) describes a group of genetic disorders that primarily affect the cell growth of neural tissues.
Three clinically and genetically distinct forms of neurofibromatosis have been described: neurofibromatosis type 1 (NF1),
neurofibromatosis type 2 (NF2) and schwannomatosis. The inheritance pattern is autosomal dominant for all three types. We
present the case of a 57 years old man, admitted to the Medical Rehabilitation Clinical Hospital Baile Felix, Romania, who was
diagnosed with spastic tetraparesis, neurofibromatosis type 1, chronic viral hepatitis B and D, hypercholesterolemia, sarcopenia
and osteoporosis. The objectives of the rehabilitation treatment were combating pain; preventing and correcting vicious postures at
rest and during activity; maintaining or increasing joint mobility; increasing the mobility of the cervical and lumbar spine;
decreasing spasticity; increasing strength of paralyzed muscles; improving motor control of paralyzed limbs; transfers re-
education, gait re-education; improving breathing; improving ADLs; maintaining autonomy; gaining daily independence;
prevention of recurrent complications and increasing the quality of life. The rehabilitation treatment was complex, performed over
a period of 2 weeks and included various physiotherapy approaches, hydrokinetotherapy, massage, occupational therapy, robotic
devices and virtual reality. It improved the patient's functional independence and quality of life. Innovations in information
technology will refine and increase the efficiency, expertise and competence of medical rehabilitation, in order to ensure comfort
for the patient and an appropriate and safe therapeutic approach.
Keywords: neurofibromatosis, robotic devices, medical rehabilitation,
Introduction
Key clinical message from extramedullary growth of spinal nerve root tumors.
Neurofibromatosis is a serious condition that can lead to The management of spinal neurofibromas consists of
tetraparesis from the rapidly growth of neurofibromas, careful observation and surgery for the most severe cases,
which cause cervical spinal compression, therefore a depending on the anatomical location, degree of invasion
combined neurosurgical and medical rehabilitation early and risk of recurrence at the surgical site (4).
approach may improve the outcome and long term quality The purpose of this report is to present a case of spinal
of life in patients with NF1. neurofibromatosis focusing on usage of robotic devises in
Introduction rehabilitation management.
The term neurofibromatosis (NF) describes a group of Case presentation
genetic disorders that primarily affect the cell growth of We present the case of a 57 years old male, admitted to
neural tissues (1). Three clinically and genetically distinct the Medical Rehabilitation Clinical Hospital Baile Felix,
forms of neurofibromatosis have been described: Romania based on the following symptoms: orthostatism
neurofibromatosis type 1 (NF1), neurofibromatosis type 2 and gait deficiency, accentuated tetramelic motor deficit,
(NF2) and schwannomatosis. The inheritance pattern is sensitive deficit, sphincter dysfunction, multiple joints
autosomal dominant for all three types (2). stiffness, neck pain, major functional deficit, activities of
NF1, also called von Recklinghausen disease, is caused by daily living(ADL) disability. The patient’s family history
pathogenic mutations of the NF1 gene, which is located revealed that his father had Von Recklinghausen's disease,
on chromosome 17q11.2 (3). The disease is characterized but it was not medically documented. From the patient’s
by specific clinical features including hyperpigmented past medical history we found that the current disease had
spots, neurofibromas, Lisch nodules, skeletal an insidious onset, at the age of 28, in 1990, with low
abnormalities and increased risk to malignancies, the back pain, severe stiffness and balance disorder. He was
effects of the mutant gene extending on multiple systems diagnosed in 1993 with NF type 1, while developing
of the body. Neurofibromas can develop from dorsal nerve intrarachidian neurofibroma (C1-C2, C3-C4, C4-C5),
roots, as well as peripheral nerves in the spinal canal. which caused medullary compression. He was operated in
Spinal tumors were observed in about 40% of patients. 1993: C3-C4 laminectomy with subtotal macroscopic
Spinal cord involvement in neurofibromatosis is typically ablation of 3 left antero-lateral tumors extended to the

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base of the skull. In 1997 he underwent surgery due to the His diagnoses were: Spastic tetraparesis (neurological
aggravation of the motor deficit, tetraparesis, hypoesthesia injury Asia C motor level C5). Neurofibromatosis type 1
in the right leg, pyramidal syndrome and sphincter (C1-C2, C3-C4 intrarachidian neurofibroma, operated,
dysfunction. The extension of laminectomy to C3 with recurrent, re-operated). Chronic viral hepatitis B and D.
scar excision was performed. On September 2003 the Hypercholesterolemia. Sarcopenia. Osteoporosis.
patient was admitted again into the neurosurgical The treatment strategies included medical treatment:
department with worsening of symptoms and the excision hypocholesterolemic dietary regime; nootropic
of the scar was performed once again. A contrast MRI of medication, antioxidant medication, psychoaffective
the dorsal spine performed in 2015 showed multiple support medication, epilepsy prophylaxis, and medical
neurofibromas along the cervical and dorsal nerves, with rehabilitation.
stenosis of the cervical spinal canal and medullary and The objectives of rehabilitation treatment were combating
bulbar compression. In 2017 he was admitted again into pain; preventing and correcting vicious postures at rest
the neurosurgical department with progressive tetraparesis and during activity; maintaining or increasing joint
and gait deficiency, he underwent microscopic ablation of mobility; increasing the mobility of the cervical and
the tumor formation from root level C2 through posterior lumbar spine; decreasing spasticity; increasing strength of
cervical approach. He also reported having pulmonary paralyzed muscles; improving motor control of paralyzed
neurofibroma, bilateral neurosensory hearing loss, limbs; transfers re-education, gait re-education; improving
uncomplicated sigmoid diverticulosis. breathing; improving ADLs; maintaining autonomy;
The general physical examination revelead asthenic gaining daily independence; prevention of recurrent
constitution, over 6 café-au-lait spots on the trunk and complications (constipation, epileptic seizures, risk of
extremities, skinfold freckling, laterocervical and fractures, urinary tract infections) and increasing the
posterior cervical postoperative keloid scar, cervical spine quality of life.
hypomobility and urgent urination. The musculoskeletal The rehabilitation treatment was complex, performed over
system evaluation revealed: ambulation in a wheelchair a period of 2 weeks and included various physiotherapy
over short distances, could not maintain orthostatism, approaches: hydrokinetotherapy in the pool: 36oC, 20
bilateral "claw" hand, incomplete left eyelid ptosis, left minutes daily; massage; occupational therapy; robotic
miosis, left enophthalmia (Claude-Bernard-Horner devices; virtual reality.
syndrome), dorsal paravertebral tumors, fasciculations in In order to decrease spasticity, neuroproprioceptive
the right pectoralis muscle and in the deltoid muscle facilitation techniques were recommended: slow and
bilaterally, in the biceps brachii, triceps brachii and sustained muscle stretching, rhythmic initiation, slow
suprascapular muscles bilaterally, bilateral reversals with opposition.
sternocleidomastoid muscles atrophy. Muscle strength To increase muscle strength in the upper limbs isometric
was 4/5 in the both upper limbs, and 3/5 in both lower and isotonic resistance active movements were
limbs. Evaluation of muscle spasticity on the Modified recommended, and for the lower limbs assisted active
Ashworth Scale revealed 1 for the upper limbs and 3 for movements for performing the entire movement trip, then
the lower limbs. Other findings were: hammer toes; manual resistance movements, isometric exercises for
pyramidal syndrome; tibio-tarsal and bilateral radio-carpal toning the pelvic girdle.
joint stiffness; bilateral lower limb exteroceptive Re-education of wheelchair transfers was made using
hypoaesthesia; extended muscle atrophies of the chest specific techniques. Bobath ball was used for balance and
muscles, deltoid muscle, biceps and triceps muscles and coordination; gait re-education used the treadmill in
brachial suprascapular muscle; bladder incontinence straight and inclined plane.
through overflow, urgent urination. Laboratory findings To improve the respiratory amplitude, specific exercises
showed high level of serum amylase and were recommended for toning the diaphragm and the
hypercholesterolemia. thoracic muscles with the aid of small weights, then with
The cervical spine radiography showed: reversal of the gradual increasing of the weight.
profile curve with anterolisthesis C4 gr. I (5 mm) and C5 Occupational therapy had the following objectives and
preanterolisthesis and advanced inferior cervical means: prevention of deformities and vicious postures
dysarthrosis; metal clips in right paravertebral projection caused by changes in muscle tone, by using orthotics in
C6. Bilateral ankle radiography revealed incipient tarsal- daily life; inhibition of abnormal movement and posture
tibial osteoarthritis. patterns; restoring active mobility, strength and
Determination of the bone mineral density by coordination in the upper body; acquiring a maximum
osteodensitometry showed a lumbar spine Z score of -1.7, degree of functional independence in self-care; facilitating
right hip Z score was -2.4 and left hip Z score was -2.1. family reintegration by assigning occupational roles
Total lean body mass was 0.54. appropriate to current abilities; establishing a balance
between rest, lucrative and recreational activities;

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improving ADLs and increasing the quality of life by and an increased risk of malignant peripheral nerve sheath
optimizing the patient’s home environment to his tumors and connective tissue malignancies (5). Another
individual abilities. characteristic is highly variable clinical expressivity, some
Robotic-assisted gait training using the Lokomat® individuals having barely noticeable neurological
stimulated neuroplasticity by the intensely repetitive problems, while others are severely affected (6). NF1 or
movements, associated with visual, auditory and tactile von Recklinghausen's disease (named after the German
feedback. Lokomat patient report revealed that the patient pathologist, Friedrich Daniel von Recklinghausen who
improved motor control, proven by increasing of speed by described the disease in 1882) is the most common type
58% (fig. 1) and patient's personal contribution to gait and manifests at birth or during early childhood.
increased by 3% (fig. 2). Robotic assistance of Reo-Go Neurofibroma is a benign peripheral nerve sheath tumor
and Hand of Hope devices were used in upper limb which arises from Schwann cells and peripheral
reeducation, by using passive movements (flexibility, fibroblasts and constitute one of the main manifestations
mobility, reduction of spasticity), or by assisting an active of NF1 (1). They are rarely present at birth and usually
movement (the patient has active mobility but not at full appear in late childhood or early adolescence (7).
range of motion). Enlargement and deformity of bones and curvature of the
The patient benefited from two projective virtual reality spine (scoliosis) may also be present. On occasion, people
systems, one called ”Nirvana” (which also includes a with NF1 may develop tumors in the brain, on the cranial
diagnostic and testing system) and a desktop type included nerves or involving the spinal cord. Inguinal and axillary
in robotic gait therapy (Lokomat). freckles are frequently present (8).
By the end of the second week of complex rehabilitation, The patient described here is a very typical case of NF-1,
the patient had improvements in muscle strength, with multiple café-au-lait spots on the trunk and arms and
coordination and balance, and reeducation of transfers. neurofibromas. The particularity of this case is the
To assess the degree of disability and the progress the presence of multiple recurrent neurofibromas localized at
patient made during rehabilitation we used the FIM scale. the cervico-dorsal level of the spine and of a plexiform
FIM scores were tracked on admission in and discharge neurofibroma (PN) localized on the posterior wall of the
from our hospital, and it was 43 and 56, respectively. left thorax with intrathoracic extension. The investigation
Psychological therapy performed cognitive assessment, of this case was complex, in order to exclude other tumors
memory and concentration tests, psychological adjustment (9). Plexiform neurofibromas (PNs) represent an
of the patient in order to accept his deficiency, to improve uncommon variant of NF1. They can occur at any age.
communication capacity and facilitate social integration. Neurofibromas emerge from multiple nerves as bulging
and deforming masses, and involve also connective tissue
and skin folds (10). Studies of Tonsgard et al. (11) and
Schorry et al. (12) performed on 126 and 240 individuals
with NF1, respectively, have shown the frequency of PNs
and their most common sites. Most of the patients in these
two studies were asymptomatic.
Sarcopenia was added to the motor deficit, further
reducing the patient's quality of life (13,14). In the
Fig. 1. Lokomat training revealing a significant average neurological patient the presence of neck pain and low-
speed increase between the first and the last session back pain increases disability, requiring special
investigations and adjustment of the rehabilitation
treatment (15,16).
The case management required a multidisciplinary team
(17). Prevention of the risk of falling is an important goal
in this patient with motor deficit and low bone mineral
density (18). There is no medical treatment for NF1,
therefore the management must be toward prevention and
Fig. 2. Lokomat training revealing an increase of average control of the complications. The rate of malignant
body weight support between the first and the last session transformation of NF1 is low (3 – 5%), but these
The patient gave written informed consent for publication malignancies can cause other clinical problems, including
of the case. The study was performed in accordance with esthetic and functional compromising. Unfortunately,
the Declaration of Helsinki. sometimes surgical excision cannot completely remove
Discussion large or multiple lesions (1). Surgical intervention is
Neurofibromatoses are inherited tumor predisposition indicated when the patient's function is impaired. In this
syndromes that are characterized by benign neurofibromas case, the patient had had four operations, but the lesions

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recurred and because of the extent of the lesions, he had the neurological hand and gaining emotional support by
Claude Bernard syndrome. Post-surgery regrowth is also interacting with the information on the computer screen.
common, as observed in our case. Our patient has a claw hand deformity that we tried to
Our patient had significant motor deficits, such as reduced reduce by using the device that takes over the activity of
muscle mass, muscle weakness, fatigability, marked the hand and each finger through the external help
spasticity, with a progressive course over the years. These provided. It completed the physical and occupational
are recognized as common manifestations of NF1, and therapy, facilitating daily activity by using passive
have been attributed to central nervous system movements, which maintain flexibility, mobility, and at
dysfunction (19). However, recent preclinical and clinical the same time, reduces spasticity (24-26).
studies have indicated a primary role for the NF1 gene Virtual reality is an assistive device used for both upper
product, neurofibromin, in muscle growth and metabolism and lower body training, through a computer assisted
(20). rehabilitation environment in which the patient interacts
Repeated patterns of movement are an important factor within the virtual environment, performing functional or
conditioning the neuroplasticity of the human nervous game-like tasks of varying levels and difficulty. This
system. Robotic neurorehabilitation devices have been enables the therapist to determine the optimal
developed precisely to enable repetitive motor training of environmental factors for the patient. Within the
patients with important deficits. In this case, the main ”interaction space” sensations and perceptions related to
purpose of the treatment was to improve independence, the virtual experience take place: here the patient’s sense
mobility, and performing activities of daily living. This is of presence is established, and the process of assigning
usually achieved with physical and occupational therapy, meaning to the virtual experience and the actual
but in our case we also used robotic devices and virtual performance of virtual tasks or activities occur. Creating
reality. One of these devices is Lokomat, an adjustable goals in the virtual world that reproduce real life ensures re-
exoskeleton combined with a treadmill that ensures learning and re-gaining skills and lost physical functions, and it
physiologic gait pattern assistance by mobilizing the also increases the success rate of rehabilitation programs that
patient's lower limbs that cannot move without support, use the complexity of virtual reality (27,28).
detecting the patient's active contribution to limb Occupational therapy is an important part of the
mobilization, automatically adjusting throughout the rehabilitation process. It allows patients to be more social,
treatment session, balancing patient support and to use their own functions for creative jobs and to deal
participation. This device is able to deliver high amounts with psychological problems like depression (29).
of repetitions in a single therapy session, thus the patient As for other genetic conditions, the NF1 patients require
will not be tired. It is also increasingly motivational by genetic counseling and in specific cases mutation
applying audio-visual displays and games scenarios and detection can be performed using different molecular
can provide variable practice schedules at arbitrary methods (30-32). NF1 patients should be advised that the
frequencies. The device measures the patient’s effort and disorder is autosomal dominant and that the recurrence
challenges him accordingly, allowing the therapist to risk is 50% in both sexes. It is important to conduct a long-
term follow-up, because of local complications and the risk of
adjust the difficulty of the training according to the
malignant transformation. In cases with a rapid increase in the
patient's motor skills. The Lokomat device can help size of neurofibroma and presence of pain, the probability of
patients with spinal cord injuries or paralyzed by stroke malignant transformation must be considered (1).
learn to walk again. Lokomat provides what is known as
automated locomotion therapy. Its benefits have been Conclusions: The complex medical rehabilitation, which
mentioned in various studies (21-23). included upper and lower limb training robotic devices,
Robotic assistance of Reo-Go, a device used in upper limb improved the patient's functional independence and
reeducation through its screen, allows a feedback process quality of life. Virtual reality techniques are being
in which the patient is constantly informed about the developed in the field of medical rehabilitation. The
amplitude and intensity of the performed movement. It possibilities, approaches and solutions in virtual reality-
increased motivation through functional exercises and based applications are huge. Innovations in information
entertaining games for patient, improving arm function, technology will refine and increase the efficiency,
patient's well-being and independence, and trained expertise and competence of medical rehabilitation, in
activities of daily living. The device stimulates the order to ensure comfort for the patient and an appropriate
cerebral cortex and allows the restoration of functional and safe therapeutic approach.
structures and the neighboring structures, unaffected by
the disease.
Hand of Hope is a device used also in upper limb
reeducation. The robotic hand reeducation device has
beneficial results in reeducating the functional deficit of

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References: women. Journal of Environmental Protection and Ecology.
1. Ghalayani P, Saberi Z, Sardari F. Neurofibromatosis type I (von 2008;1(1):67-69.
Recklinghausen's disease): A family case report and literature 18. Feldmann R, Denecke J, Grenzebach M, Schuierer G, Weglage
review. Dent Res J (Isfahan). 2012 Jul;9(4):483-488. J. Neurofibromatosis type 1: motor and cognitive function and
2. Korf BR. Neurofibromatosis. Handb Clin Neurol. 2013 T2-weighted MRI hyperintensities. Neurology. 2003
Apr;111:333-340. Dec;61(12):1725–1728.
3. Gutmann DH, Ferner RE, Listernick RH, Korf BR, Wolters PL 19. Summers MA, Quinlan KG, Payne JM, Little DG, North KN et
et al. Neurofibromatosis type 1. Nat Rev Dis Primers. 2017 al. Skeletal muscle and motor deficits in Neurofibromatosis
Feb;3:17004. Type 1. J Musculoskelet Neuronal Interact. 2015
4. Carman Kb, Yakut A, Anlar B, Ayter S. Spinal Jun;15(2):161-170.
neurofibromatosis associated with classical neurofibromatosis 20. Nam KY, Kim HJ, Kwon BS, Park JW, Lee HJ et al. Robot-
type 1: genetic characterisation of an atypical case. BMJ Case assisted gait training (Lokomat) improves walking function and
Rep. 2013 Feb 14;2013:bcr2012008468. activity in people with spinal cord injury: a systematic review. J
5. Seminog OO, Goldacre MJ. Risk of benign tumours of nervous Neuroeng Rehabil. 2017 Mar;14(1):24.
system, and of malignant neoplasms, in people with 21. van Kammen K, Boonstra AM, van der Woude LHV, Visscher
neurofibromatosis: population-based record-linkage study. Br J C, Reinders-Messelink HA et al. Lokomat guided gait in
Cancer. 2013 Jan;108(1):193–198. hemiparetic stroke patients: the effects of training parameters
6. Sabbagh A, Pasmant E, Laurendeau I, Parfait B, Barbarot S et on muscle activity and temporal symmetry. Disabil Rehabil.
al. Unravelling the genetic basis of variable clinical expression 2020 Oct;42(21):2977-2985.
in neurofibromatosis 1. Hum Mol Genet. 2009 22. van Silfhout L, Váňa Z, Pĕtioký J, Edwards MJR, Bartels
Aug;18(15):2768-2778. RHMA et al. Highest ambulatory speed using Lokomat gait
7. Cunha KS, Barboza EP, Dias EP, Oliveira FM. training for individuals with a motor-complete spinal cord
Neurofibromatosis type I with periodontal manifestation. A injury: a clinical pilot study. Acta Neurochir (Wien). 2020
case report and literature review. Br Dent J. 2004 Apr;162(4):951-956.
Apr;196(8):457-60. 23. Casadio M. Giannoni P. Morasso P. Sanguineti V. A proof of
8. Stoicanescu LD, Cevei ML, Sirbu EM, Zdrinca MM, Mutiu G. concept study for the integration of robot therapy with
Unusual occurrence of avascular necrosis with bilateral physiotherapy în the treatment of stroke patients. Clin Rehabil.
involvement and ankylosing spondylitis, meningioma and 2009 Mar;23(3):217-228.
Hodgkin lymphoma. Rom J Morphol Embryol. 2019 Jul- 24. Krebs HI, Krams M, Agrafiotis DK, DiBernardo A, Chavez JC
Sept:60(3):1003-1007. et al. Robotic measurement of arm movements after stroke
9. Tchernev G, Chokoeva AA, Patterson JW, Bakardzhiev I, establishes biomarkers of motor recovery. Stroke. 2014
Wollina U et al. Plexiform Neurofibroma: A Case Report. Jan;45(1):200–204.
Medicine (Baltimore). 2016 Feb;95(6):e2663. 25. Miller EL, Murray L, Richards L, Zorowitz RD, Bakas T et al.
10. Tonsgard JH, Kwak SM, Short MP, Dachman AH. CT imaging Comprehensive overview of nursing and interdisciplinary
in adults with neurofibromatosis-1. Frequent asymptomatic rehabilitation care of the stroke patient: a scientific statement
plexiform lesions. Neurology. 1998 Jun;50(6):1755-60. from the American heart association. Stroke. 2010
11. Schorry EK, Crawford AH, Egelhoff JC, Lovell AM, Saal HM. Oct;41(10):2402-2448.
Thoracic tumors in children with neurofibromatosis 1. Am J 26. Kizony R, Katz N, Weiss PL. Virtual reality based intervention
Med Genet. 1997 Sept;74(5):533- 537. in rehabilitation: relationship between motor and cognitive
12. Cevei M, Onofrei RR, Cioara F, Stoicanescu D. Correlations abilities and performance within virtual environments for
between the Quality of Life Domains and Clinical Variables in patients with stroke. Proc 5th Int Conf Disability, Virtual
Sarcopenic Osteoporotic Postmenopausal Women. J. Clin. Med. Reality and Assoc. Tech. Oxford, UK. 2004:19-26.
2020 Feb;9(2):441 27. Maggio MG, Torrisi M, Buda A, De Luca R, Piazzitta D et al.
13. Hodinka L, Vereckei E, Gasparik AI. Sarcopenia és Effects of robotic neurorehabilitation through lokomat plus
életminőség: a Sarcopenia Quality of Life (SarQoL) kérdőív virtual reality on cognitive function in patients with traumatic
hiteles magyar fordítása [Sarcopenia and quality of life: the brain injury: A retrospective case-control study. Int J Neurosci.
validated Hungarian translation of the Sarcopenia Quality of 2020 Feb;130(2):117-123.
Life (SarQoL) questionnaire]. Orv Hetil. 2018 28. Nas K, Yazmalar L, Şah V, Aydın A, Öneş K. Rehabilitation of
Sep;159(36):1483-1486. spinal cord injuries. World J Orthop. 2015 Jan;6(1):8-16.
14. Sirbu E, Onofrei R, Szasz S, Susan M. Predictors of disability 29. Ly KI, Blakeley JO. The Diagnosis and Management of
in patients with chronic low back pain. Archives of Medical Neurofibromatosis Type 1. Med Clin North Am. 2019
Science. 2020 Jul. https://doi.org/10.5114/aoms.2020.97057 Nov;103(6):1035-1054.
15. Cevei M, .Roşca E, Lazar L, Muţiu G, Stoicănescu D et al. 30. Gug C, Stoicanescu D, Mozos I, Nussbaum L, Cevei M et al.
Imagistic and histopathologic concordances in degenerative De Novo 8p21.3→p23.3 Duplication with t(4;8)(q35;p21.3)
lesions of intervertebral disks. Rom J Morphol Embryol. 2011 Translocation associated with Mental Retardation, Autism
Jan-March; 52 (1 Suppl):327-332. Spectrum Disorder and Congenital Heart Defects: Case Report
16. Roman N, Tirziman E, Sorea D, Miclaus R, Repanovici A et al. With Literature Review. Front. Pediatr. 2020 Jul; 8:375.
Ethical Dilemmas in the Interdisciplinary Approach to 31. Gug C, Gorduza EV, Lăcătuşu A, Vaida MA, Bîrsăşteanu F et
Informed Consent to Patients in Physiotherapy Services in al: CHARGE syndrome associated with de novo (I1460Rfs*15)
Romania. Revista de Cercetare si Interventie Sociala. 2018 frameshift mutation of CHD7 gene in a patient with arteria
Dec;63:290-303. lusoria and horseshoe kidney. Exp Ther Med. 2020 Jul;20:479-
17. Moga M, Preda G, Marceanu L, Miclaus R, Bagiu N. Lifestyle 485.00
factors related to bone mineral density in postmenopausal

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