Ital. J. Neurol. Sci. 13:259-263, 1992
Giant congenital nevus and chronic progressive ascending hemiparesis (Mills syndrome). Report of a case Frisoni G.B.,* Gasparotti R.,** Di Monda V.* * Clinica Neurologica, Universitgt di Brescia ** Istituto di Radiologia, Universit~ di Brescia
We describe the case of a 20year oM boy with a giant congenital nevus who developed a chronic progressive ascending hemiparesis. The association of the pigmented lesion with a focal neurological deficit is pathognomonic for neurocutaneous melanosis complicated by a leptomeningeal melanoma. MR imaging at 1.5 tesla ruled out such a possibility and showed a small aspecific pontine lesion along the route of the corticospinal tract. We discuss possible etiologies.
Key Words: Giant nevus - - Mills syndrome - - neurocutaneous melanosis - - primary lateral sclerosis - - phakomatosis - - chronic hemiparesis.
Introduction
Case report
Giant congenital nevi are rare pigmented cutaneous lesions that are evident at birth (200 cases reported up to 1965) [9]. In a rare phakomatosis called neurocutaneous melanosis ( N C M ) they are associated with leptomenigeal melanosis. When uncomplicated, N C M presents with various aspecific neurological symptoms, such as those due to hydrocephalus, to a chronic basal meningitis, or seizures [3]. On the other hand, the association of a giant congenital nevus with a focal neurological deficit is always fatal, being due to N C M complicating with a malignant leptomeningeal melanoma. Mills syndrome is a disputed clinical entity, which is characterized by a chronic slowly progressing spastic ascending hemiparesis and can be due to a number of diseases. We describe here a patient with a giant congenital nevus and a focal neurological deficit (a right Mills syndrome), detected with a 1.5 tesla magnetic resonance images, which was probably due to a small non-melanotic lesion in the controlateral ventral pons.
The patient is a 20-year-old white m a n with high school education, who was born with a giant nevus on his back and shoulders, and a n u m b e r o f other minor nevi scattered on the limbs and face (Figs. 1 and 2). The size o f these pigmented lesions did not increase with age, b e y o n d the rate o f normal b o d y growth. When he was about 6 years of age, his parents realized that he could not walk properly, and he himself remembers that his right lower limb was weaker than the left. The strenght deficit gradually increased as he grew older; after a few years a sural clonus appeared. At 11 years o f age a CT scan was reported to be normal. At 13 years o f age myelography, standard C S F examination, including electrophoresis and Link index, and another CT scan were all normal. Weakness of the right u p p e r limb did not progress significantly. Speech was normal. The patient did not abuse o f alcohol or other drugs. The strenght deficit had never impaired his physical activity. On admission the patient was 188 cm tall, weighed 74 kg, and a p p e a r e d o f normal intelli-
Received 27 September 1990 - Accepted 2 July 1991
259
The Italian Journal of Neurological Sciences
Fig. I. Front view of the patient.
Fig. 2. Back view of the patient.
gence. A very large nevus was present on much of the trunk, involving the whole back including the nuchal region, the lateral aspects of the trunk and the lateral parts of chest and abdomen, sparing only an irregular zone around the anterior sagittal midline, which was smaller on the chest and larger on the abdomen (Figs. 1 and 2). The nevus was highly pigmented and hairy cranially, less pigmented and hairless caudally. A soft, drooping, less pigmented mass, was present on the back, involving the midline and extending to the left from the IV to the VII thoracic vertebrae (Fig. 3). The patient refused biopsy of this lesion. Many other nevi, some of which were hairy, were scattered on his face and limbs, ranging from 1 to 10 cm in diameter. Gait was moderately pareticspastic on the right. A mild right lower facial
nerve palsy was present. Strength was normal in the upper limbs, and only mildly decreased in the fight lower limb [4/5 on the Medical Research Council (M.R.C.) Scale]. Fine movements were clumsily performed with the fight hand. In the fight limbs muscle tone was moderately increased, deep tendon reflexes were brisk and both sural an patellar clonus could be easily elicited. Right limbs were also mildly hypotrophic, but without fasciculations. Babinski and Hoffman signs were present only on the right. There were no sensory deficits. Blood and urine tests were normal. EEG and E M G were both normal. A S P E C T brain scan using radioactive Tc PAO showed normal cerebral perfusion, Visual, acoustic and somatosensory evoked potentials were all normal. The patient
260
Frisoni G.B.: Giant congenital nevus and Mills syndrome
refused a further lumbar puncture. On MR imaging with a 0.5 tesla superconductive unit (Philips Gyroscan S 5), capable of performing inversion recovery and spin echo sequences, the brain and spinal cord were normal. MR imaging was then performed with a 1.5 superconductive unit (Magnetom Siemens, Erlangen). T1, T2 and proton density weighted images were obtained with a flow-compensated spin-echo sequence (5002300 / 15-90 ( 1-2 TR range / TE range / excitations) on the axial, sagittal and coronal planes. The whole brain was studied with a slice thickness of 4 mm and 20% gap between slices. MR showed a small area of signal alteration with a lengthening ofT2 relaxation time, hyperintense in T2-weighted axial images located in the left anterior aspect of the pons, in the region of the corticospinal tract (Fig. 4). This focal lesion was about 2 mm in diameter in the axial sections. Sagittal and coronal T2-weighted images were useful in defining the extent, the morphology and the exact site of the lesion, which appeared as a thin band of signal hyperintensity in the anterior aspect of the pons, along the route of the corticospinal tract fibers and extending from the medullopontine junction to the upper third of the pons (Figs. 5 and 6). Proton density weighted images showed no alteration of signal intensity, while in Tl-weighted images the lesion, though less apparent, was mildly hypointense with a lengthening of T1 relaxation time. The sigr,_al intensity characteristics were aspecific. No other abnormal signal could be detected.
Fig. 4. T2-weighted axial image o f the lower pons. The arrow shows the lesion.
Discussion
Giant congenital nevi are pigmented cutaneous lesions, involving the trunk with a "bathing suit" or "cape" distribution, often hairy and some-
Fig. 5. T2-weighted sagittal images. Median section is at the top and left paramedian section is at the bottom o f the figure.
Fig. 3. The soft, less pigmented drooping mass within the nevus.
times verrucous and pachydermic [10]; they tend to have a dermatome distribution and to originate from the posterior midline [9]. Reed et al. [9] found that in patients with giant congenital nevus, leptomeningeal involvement and related neurological symptoms were more frequent when the cutaneous lesion extended to the scalp or to the nuchal region. The pigmented lesions do not enlarge with increasing age beyond the rate of normal body growth. Neurocutaneous melanosis is the rarest of the 261
The Italian Journal of Neurological Sciences
Fig. 6. T2-weightedcoronal image. phakomatoses or neurocutaneous diseases [6], only 78 cases having been reported up to now. NCM is characterized by the association of pigmented cutaneous and central nervous system lesion; it is a congenital but not hereditary disease, and has no sex prevalence. All patients have abnormal skin pigmentation, the commonest lesions being the giant congenital nevus and other large nevi. The most typical lesion of the central nervous system is leptomeningeal melanosis; this is a focal, multifocal or diffuse excess of melanocytes in the pia mater and in the subarachnoid space. Melanosis is more frequent and marked at the skull base. A primary leptomeningeal melanoma, heralded by a focal neurological deficit, developed in about one third of the reported cases of NCM, most often in infants, children and adolescents [4]. A unilateral, progressive, ascending paralysis with pyramidal signs was first described in 1900 by Mills [8], who proposed it to be a new form of degenerative disease. The eponym "Mills syndrome" then gained ground to designate the hemiplegic variant of amyotrophic lateral sclerosis, but it is now seldom found in the neurological literature, only two works on "Mills syndrome" having been published in the last 15 years in major neurological journals [2, 7]. As suggested by Malin et al. [7], Mills syndrome is probably an obsolete clinical term, concealing diseases such as amyotrophic lateral sclerosis, multiple sclerosis, parkinsonism or syphilis. A progressive ascending paralysis with pyramidal signs in the absence of lower motor neuron involvement, due to primary and selective degeneration of the corticospinal tract, is known as primary lateral sclerosis (PLS). PLS is a debated en262
tity which only recently has attained the status of a separate entity [5, 10]. It involves both lower limbs and spreads as time passes to the upper limbs ["syndrome of spastic paraparesis of middle life" [10], it is sometimes accompanied by cortical atrophy [1], and must be distinguished from multiple sclerosis, amyotrophic lateral sclerosis, leukoencephalopathy, Chiari malformation, syringomyelia, structural lesions or tumors of the skull base. Our patient presents a congenital giant nevus with typical distribution extending to the nuchal region and associated with a gross focal neurological deficit in the form of a slowly progressive right hemiparesis. This association is highly suggestive of neurocutaneous melanosis, which deserves due consideration in view of the high frequency of primary intracranial melanomas. The pathognomonic MR imaging of melanin deposits is both T1 and T2 hyperintensity, due to the paramagnetic properties of the molecule. In our patient MR imaging ruled out an intracranial neoplasm, but also did not show any signal abnormality, either in the cerebral tissue or in the surrounding meninges, suggestive of melanin deposition. This could be due either to actual absence of melanin deposits or melanin-laden cells, or to failure to show microscopic deposits. To our knowledge, the association of a focal neurological deficit in the absence of a leptomeningeal melanoma or of gross anomalies of the brain is a finding never described before. The small pontine lesion detected by MRI is highly likely to be responsible for the patient's neurological deficit, being restricted to the left pyramidal pathway before its crossing. The signal characteristics are however aspecific, being common to a number of pathological conditions. The possibility that such a lesion is due to one of the four diseases found associated with Mills syndrome, i.e. Parkinson disease, multiple sclerosis, amyotrohic lateral sclerosis and syphilis, as well as to cerebrovascular disease [2], can be ruled out on clinical and laboratory grounds. Gliosis due to viral or bacterial infection is compatible with MR findings, but is unlikely in view of the unique focal lesion, of the negative blood and CSF findings and of the slowly progressive course. PLS can also be ruled out, given the young age of our patient, the unilateral involvement and the absence of cortical atrophy on MR imaging. In conclusion, the present case report. suggests that focal neurological signs may be associated with a giant cutaneous nevus without MRI evidence of melanotic deposits or of malignant melanoma. The etiology of the pathological involvement as detected by MR imaging and fully consistent with the clinical signs, remains unexplained in our patient.
Frisoni G.B.: Giant congenital nevus and Mills syndrome
Acknowledgement:We wish to thank Dr. Stefano F. Cappa for helpful suggestions during the preparation of the manuscript and for its revision, Dr. Paolo Guerra for performing the SPECT examination and Dr. Giorgio Pasolini for valuable dermatological counselling.
Sommario Descriviamo il caso di un ragazzo di 20 anni con un nevo congenito gigante che ha sviluppato una emparesi ascendente progressiva cronica. L'associazione della lesione pigmentata ad un deficit neurologico focale k patognomonica della melanosi neurocutanea complicata da un melanoma leptomeningeo. L 'imaging con Risonanza Magnetica a 1.5 Tesla ha permesso di escludere questa possibilith ed ha dimostrato una piccola ed aspecifica lesione pontina lungo il decorso del tratto corticospinale. Discutiamo quindi le possibili cause eziologiche.
Address reprint requests to: Dr. G i o v a n n i B. Frisoni Via 2 Giugno, 3 25045 Castegnato-BS
References [l] BEAL M.F., RICHARDSON E.P.: I~'mary lateral sclerosis: a case report. Arch. Neurol. 38:630-633, 1986. [2] DALLAVOLTA G., MAGONI M., VANGI D., WIGNOLO L. : Role of M R l in the diagnosis of Mills sydnrome. Ital. J. Neurol. Sci 10:519-521, 1989. [3] Fox H.: Neuroeutaneous melanosis. In: Vinken P.J. and Bruyn G.W. eds. Handbook of Clinical Neurology. The Phakomatoses; vol. 14. Amsterdam, North-Holland, pp. 414-428, 1972. [4] GUIDETFI V., GARCOVICHA., GIUFFRI~R., CURATOLO P. : Nevo gigante congenito e melanosi neurocutanea. Considerazioni su due casi clinici. Min. Ped. 30:1961-1972, 1978. [5] GRUNNETI" M.L., LEICHER C., ZIMMERMAN A., ZALNERAITIS E., BARWICK M.: Primary lateral sclerosis in a child. Neurology 39:1530-1532, 1989. [6] LEANLYB.J., ROWE P.W., KLUG G.L.: N e u r o c u t a -
[7]
[8]
[9]
[10]
neous melanosis with hydrocephalus and syringomyelia. J. Neurosurg. 62:148-152, 1985. MALIN J.P., POBURSKI R., REUSC~E E.: Klinische Varianten der amyotrophen Lateralsklerose: hemiplegischer Typ der ALS und Mills-Syndrom. Ein kritischer Rfickblick. Fortschr. Neurol. Psichiat. 54:101-105, 1986. MILLs C.K. :A case of unilateral progressive ascending paralysis, probably representing a new forrn of degenerative disease. J. Nerv. Ment. Dis. 27:195200, 1900. REED W.B., BECKER SR S.W., BECKER JR S.W., NICKEL W.R.: Giant pigmented nevL melanoma and leptomeningeal melanocytosis. Arch. Derm. 91:100-119, 1965. YOUNGER D.S., CHOU S., HAYS A.P., LANG D.J., EMESON R., BRIN M., THOMPSON H., ROWLAND L.P. : Primary lateral sclerosis: a clinical diagnosis reemerges. Arch. Neurol. 45:1304-1307, 1988.
263
Giant congenital nevus and chronic progressive ascending hemiparesis (Mills syndrome). Report of a case Frisoni G.B.,* Gasparotti R.,** Di Monda V.* * Clinica Neurologica, Universitgt di Brescia ** Istituto di Radiologia, Universit~ di Brescia
We describe the case of a 20year oM boy with a giant congenital nevus who developed a chronic progressive ascending hemiparesis. The association of the pigmented lesion with a focal neurological deficit is pathognomonic for neurocutaneous melanosis complicated by a leptomeningeal melanoma. MR imaging at 1.5 tesla ruled out such a possibility and showed a small aspecific pontine lesion along the route of the corticospinal tract. We discuss possible etiologies.
Key Words: Giant nevus - - Mills syndrome - - neurocutaneous melanosis - - primary lateral sclerosis - - phakomatosis - - chronic hemiparesis.
Introduction
Case report
Giant congenital nevi are rare pigmented cutaneous lesions that are evident at birth (200 cases reported up to 1965) [9]. In a rare phakomatosis called neurocutaneous melanosis ( N C M ) they are associated with leptomenigeal melanosis. When uncomplicated, N C M presents with various aspecific neurological symptoms, such as those due to hydrocephalus, to a chronic basal meningitis, or seizures [3]. On the other hand, the association of a giant congenital nevus with a focal neurological deficit is always fatal, being due to N C M complicating with a malignant leptomeningeal melanoma. Mills syndrome is a disputed clinical entity, which is characterized by a chronic slowly progressing spastic ascending hemiparesis and can be due to a number of diseases. We describe here a patient with a giant congenital nevus and a focal neurological deficit (a right Mills syndrome), detected with a 1.5 tesla magnetic resonance images, which was probably due to a small non-melanotic lesion in the controlateral ventral pons.
The patient is a 20-year-old white m a n with high school education, who was born with a giant nevus on his back and shoulders, and a n u m b e r o f other minor nevi scattered on the limbs and face (Figs. 1 and 2). The size o f these pigmented lesions did not increase with age, b e y o n d the rate o f normal b o d y growth. When he was about 6 years of age, his parents realized that he could not walk properly, and he himself remembers that his right lower limb was weaker than the left. The strenght deficit gradually increased as he grew older; after a few years a sural clonus appeared. At 11 years o f age a CT scan was reported to be normal. At 13 years o f age myelography, standard C S F examination, including electrophoresis and Link index, and another CT scan were all normal. Weakness of the right u p p e r limb did not progress significantly. Speech was normal. The patient did not abuse o f alcohol or other drugs. The strenght deficit had never impaired his physical activity. On admission the patient was 188 cm tall, weighed 74 kg, and a p p e a r e d o f normal intelli-
Received 27 September 1990 - Accepted 2 July 1991
259
The Italian Journal of Neurological Sciences
Fig. I. Front view of the patient.
Fig. 2. Back view of the patient.
gence. A very large nevus was present on much of the trunk, involving the whole back including the nuchal region, the lateral aspects of the trunk and the lateral parts of chest and abdomen, sparing only an irregular zone around the anterior sagittal midline, which was smaller on the chest and larger on the abdomen (Figs. 1 and 2). The nevus was highly pigmented and hairy cranially, less pigmented and hairless caudally. A soft, drooping, less pigmented mass, was present on the back, involving the midline and extending to the left from the IV to the VII thoracic vertebrae (Fig. 3). The patient refused biopsy of this lesion. Many other nevi, some of which were hairy, were scattered on his face and limbs, ranging from 1 to 10 cm in diameter. Gait was moderately pareticspastic on the right. A mild right lower facial
nerve palsy was present. Strength was normal in the upper limbs, and only mildly decreased in the fight lower limb [4/5 on the Medical Research Council (M.R.C.) Scale]. Fine movements were clumsily performed with the fight hand. In the fight limbs muscle tone was moderately increased, deep tendon reflexes were brisk and both sural an patellar clonus could be easily elicited. Right limbs were also mildly hypotrophic, but without fasciculations. Babinski and Hoffman signs were present only on the right. There were no sensory deficits. Blood and urine tests were normal. EEG and E M G were both normal. A S P E C T brain scan using radioactive Tc PAO showed normal cerebral perfusion, Visual, acoustic and somatosensory evoked potentials were all normal. The patient
260
Frisoni G.B.: Giant congenital nevus and Mills syndrome
refused a further lumbar puncture. On MR imaging with a 0.5 tesla superconductive unit (Philips Gyroscan S 5), capable of performing inversion recovery and spin echo sequences, the brain and spinal cord were normal. MR imaging was then performed with a 1.5 superconductive unit (Magnetom Siemens, Erlangen). T1, T2 and proton density weighted images were obtained with a flow-compensated spin-echo sequence (5002300 / 15-90 ( 1-2 TR range / TE range / excitations) on the axial, sagittal and coronal planes. The whole brain was studied with a slice thickness of 4 mm and 20% gap between slices. MR showed a small area of signal alteration with a lengthening ofT2 relaxation time, hyperintense in T2-weighted axial images located in the left anterior aspect of the pons, in the region of the corticospinal tract (Fig. 4). This focal lesion was about 2 mm in diameter in the axial sections. Sagittal and coronal T2-weighted images were useful in defining the extent, the morphology and the exact site of the lesion, which appeared as a thin band of signal hyperintensity in the anterior aspect of the pons, along the route of the corticospinal tract fibers and extending from the medullopontine junction to the upper third of the pons (Figs. 5 and 6). Proton density weighted images showed no alteration of signal intensity, while in Tl-weighted images the lesion, though less apparent, was mildly hypointense with a lengthening of T1 relaxation time. The sigr,_al intensity characteristics were aspecific. No other abnormal signal could be detected.
Fig. 4. T2-weighted axial image o f the lower pons. The arrow shows the lesion.
Discussion
Giant congenital nevi are pigmented cutaneous lesions, involving the trunk with a "bathing suit" or "cape" distribution, often hairy and some-
Fig. 5. T2-weighted sagittal images. Median section is at the top and left paramedian section is at the bottom o f the figure.
Fig. 3. The soft, less pigmented drooping mass within the nevus.
times verrucous and pachydermic [10]; they tend to have a dermatome distribution and to originate from the posterior midline [9]. Reed et al. [9] found that in patients with giant congenital nevus, leptomeningeal involvement and related neurological symptoms were more frequent when the cutaneous lesion extended to the scalp or to the nuchal region. The pigmented lesions do not enlarge with increasing age beyond the rate of normal body growth. Neurocutaneous melanosis is the rarest of the 261
The Italian Journal of Neurological Sciences
Fig. 6. T2-weightedcoronal image. phakomatoses or neurocutaneous diseases [6], only 78 cases having been reported up to now. NCM is characterized by the association of pigmented cutaneous and central nervous system lesion; it is a congenital but not hereditary disease, and has no sex prevalence. All patients have abnormal skin pigmentation, the commonest lesions being the giant congenital nevus and other large nevi. The most typical lesion of the central nervous system is leptomeningeal melanosis; this is a focal, multifocal or diffuse excess of melanocytes in the pia mater and in the subarachnoid space. Melanosis is more frequent and marked at the skull base. A primary leptomeningeal melanoma, heralded by a focal neurological deficit, developed in about one third of the reported cases of NCM, most often in infants, children and adolescents [4]. A unilateral, progressive, ascending paralysis with pyramidal signs was first described in 1900 by Mills [8], who proposed it to be a new form of degenerative disease. The eponym "Mills syndrome" then gained ground to designate the hemiplegic variant of amyotrophic lateral sclerosis, but it is now seldom found in the neurological literature, only two works on "Mills syndrome" having been published in the last 15 years in major neurological journals [2, 7]. As suggested by Malin et al. [7], Mills syndrome is probably an obsolete clinical term, concealing diseases such as amyotrophic lateral sclerosis, multiple sclerosis, parkinsonism or syphilis. A progressive ascending paralysis with pyramidal signs in the absence of lower motor neuron involvement, due to primary and selective degeneration of the corticospinal tract, is known as primary lateral sclerosis (PLS). PLS is a debated en262
tity which only recently has attained the status of a separate entity [5, 10]. It involves both lower limbs and spreads as time passes to the upper limbs ["syndrome of spastic paraparesis of middle life" [10], it is sometimes accompanied by cortical atrophy [1], and must be distinguished from multiple sclerosis, amyotrophic lateral sclerosis, leukoencephalopathy, Chiari malformation, syringomyelia, structural lesions or tumors of the skull base. Our patient presents a congenital giant nevus with typical distribution extending to the nuchal region and associated with a gross focal neurological deficit in the form of a slowly progressive right hemiparesis. This association is highly suggestive of neurocutaneous melanosis, which deserves due consideration in view of the high frequency of primary intracranial melanomas. The pathognomonic MR imaging of melanin deposits is both T1 and T2 hyperintensity, due to the paramagnetic properties of the molecule. In our patient MR imaging ruled out an intracranial neoplasm, but also did not show any signal abnormality, either in the cerebral tissue or in the surrounding meninges, suggestive of melanin deposition. This could be due either to actual absence of melanin deposits or melanin-laden cells, or to failure to show microscopic deposits. To our knowledge, the association of a focal neurological deficit in the absence of a leptomeningeal melanoma or of gross anomalies of the brain is a finding never described before. The small pontine lesion detected by MRI is highly likely to be responsible for the patient's neurological deficit, being restricted to the left pyramidal pathway before its crossing. The signal characteristics are however aspecific, being common to a number of pathological conditions. The possibility that such a lesion is due to one of the four diseases found associated with Mills syndrome, i.e. Parkinson disease, multiple sclerosis, amyotrohic lateral sclerosis and syphilis, as well as to cerebrovascular disease [2], can be ruled out on clinical and laboratory grounds. Gliosis due to viral or bacterial infection is compatible with MR findings, but is unlikely in view of the unique focal lesion, of the negative blood and CSF findings and of the slowly progressive course. PLS can also be ruled out, given the young age of our patient, the unilateral involvement and the absence of cortical atrophy on MR imaging. In conclusion, the present case report. suggests that focal neurological signs may be associated with a giant cutaneous nevus without MRI evidence of melanotic deposits or of malignant melanoma. The etiology of the pathological involvement as detected by MR imaging and fully consistent with the clinical signs, remains unexplained in our patient.
Frisoni G.B.: Giant congenital nevus and Mills syndrome
Acknowledgement:We wish to thank Dr. Stefano F. Cappa for helpful suggestions during the preparation of the manuscript and for its revision, Dr. Paolo Guerra for performing the SPECT examination and Dr. Giorgio Pasolini for valuable dermatological counselling.
Sommario Descriviamo il caso di un ragazzo di 20 anni con un nevo congenito gigante che ha sviluppato una emparesi ascendente progressiva cronica. L'associazione della lesione pigmentata ad un deficit neurologico focale k patognomonica della melanosi neurocutanea complicata da un melanoma leptomeningeo. L 'imaging con Risonanza Magnetica a 1.5 Tesla ha permesso di escludere questa possibilith ed ha dimostrato una piccola ed aspecifica lesione pontina lungo il decorso del tratto corticospinale. Discutiamo quindi le possibili cause eziologiche.
Address reprint requests to: Dr. G i o v a n n i B. Frisoni Via 2 Giugno, 3 25045 Castegnato-BS
References [l] BEAL M.F., RICHARDSON E.P.: I~'mary lateral sclerosis: a case report. Arch. Neurol. 38:630-633, 1986. [2] DALLAVOLTA G., MAGONI M., VANGI D., WIGNOLO L. : Role of M R l in the diagnosis of Mills sydnrome. Ital. J. Neurol. Sci 10:519-521, 1989. [3] Fox H.: Neuroeutaneous melanosis. In: Vinken P.J. and Bruyn G.W. eds. Handbook of Clinical Neurology. The Phakomatoses; vol. 14. Amsterdam, North-Holland, pp. 414-428, 1972. [4] GUIDETFI V., GARCOVICHA., GIUFFRI~R., CURATOLO P. : Nevo gigante congenito e melanosi neurocutanea. Considerazioni su due casi clinici. Min. Ped. 30:1961-1972, 1978. [5] GRUNNETI" M.L., LEICHER C., ZIMMERMAN A., ZALNERAITIS E., BARWICK M.: Primary lateral sclerosis in a child. Neurology 39:1530-1532, 1989. [6] LEANLYB.J., ROWE P.W., KLUG G.L.: N e u r o c u t a -
[7]
[8]
[9]
[10]
neous melanosis with hydrocephalus and syringomyelia. J. Neurosurg. 62:148-152, 1985. MALIN J.P., POBURSKI R., REUSC~E E.: Klinische Varianten der amyotrophen Lateralsklerose: hemiplegischer Typ der ALS und Mills-Syndrom. Ein kritischer Rfickblick. Fortschr. Neurol. Psichiat. 54:101-105, 1986. MILLs C.K. :A case of unilateral progressive ascending paralysis, probably representing a new forrn of degenerative disease. J. Nerv. Ment. Dis. 27:195200, 1900. REED W.B., BECKER SR S.W., BECKER JR S.W., NICKEL W.R.: Giant pigmented nevL melanoma and leptomeningeal melanocytosis. Arch. Derm. 91:100-119, 1965. YOUNGER D.S., CHOU S., HAYS A.P., LANG D.J., EMESON R., BRIN M., THOMPSON H., ROWLAND L.P. : Primary lateral sclerosis: a clinical diagnosis reemerges. Arch. Neurol. 45:1304-1307, 1988.
263
![[Congenital giant nevus: report of a case].](/assets/img/hold.png)
